Original Article
Efficacy of the Anti-CD22 Recombinant Immunotoxin BL22 in Chemotherapy-Resistant Hairy-Cell Leukemia
N Engl J Med 2001; 345:241-247July 26, 2001
- Abstract
Background
Hairy-cell leukemia that is resistant to treatment with purine analogues, including cladribine, has a poor prognosis. We tested the safety and efficacy of an immunotoxin directed against a surface antigen that is strongly expressed by leukemic hairy cells.
Methods
RFB4(dsFv)-PE38 (BL22), a recombinant immunotoxin containing an anti-CD22 variable domain (Fv) fused to truncated pseudomonas exotoxin, was administered in a dose-escalation trial by intravenous infusion every other day for a total of three doses.
Results
Of 16 patients who were resistant to cladribine, 11 had a complete remission and 2 had a partial remission with BL22. The three patients who did not have a response received low doses of BL22 or had preexisting toxin-neutralizing antibodies. Of the 11 patients in complete remission, 2 had minimal residual disease in the bone marrow or blood. During a median follow-up of 16 months (range, 10 to 23), 3 of the 11 patients who had a complete response relapsed and were retreated; all of these patients had a second complete remission. In 2 of the 16 patients, a serious but completely reversible hemolytic–uremic syndrome developed during the second cycle of treatment with BL22. Common toxic effects included transient hypoalbuminemia and elevated aminotransferase levels.
Conclusions
BL22 can induce complete remissions in patients with hairy-cell leukemia that is resistant to treatment with purine analogues.
Media in This Article
Figure 1
Action of BL22 on Hairy Cells.Figure 2
Response of Patients with Pancytopenia to BL22.Article Activity
- Article
About 2 percent of cases of leukemia are of the hairy-cell type.1,2 Prominent features of the disease are splenomegaly, pancytopenia, and the presence of cells in the peripheral blood, spleen, and bone marrow with hair-like cytoplasmic projections.3,4 Splenectomy is generally only palliative,5 but interferon alfa produces a partial remission in 30 to 70 percent of patients and complete remission, often of short duration, in 5 to 10 percent.6-10 The purine analogues pentostatin (2′-deoxycoformycin) and cladribine (2-chlorodeoxyadenosine) induce complete remissions in up to 85 percent of patients and partial responses in 5 to 25 percent. With such treatment, the rate of disease-free survival at eight years is 60 to 75 percent.10-13 However, patients with cladribine-resistant disease have poor responses to other therapy. In the 20 percent of patients with a variant form of hairy-cell leukemia, there are high numbers of circulating hairy cells, and the response to pentostatin or cladribine is poor.12,14
Classic or variant hairy cells are virtually always strongly positive for CD22, an adhesion molecule expressed exclusively on B cells.15-19 To target CD22-expressing cells, we designed a recombinant immunotoxin, RFB4(dsFv)-PE38 (BL22), that contains the variable domain (Fv) of the anti-CD22 monoclonal antibody RFB4.20,21 The Fv is fused to a fragment of pseudomonas exotoxin called PE38, which contains domains responsible for cell death but lacks the domain necessary for cell binding (Figure 1Figure 1
Action of BL22 on Hairy Cells.).22 BL22 induced complete remissions in mice with a B-cell lymphoma and killed fresh human malignant B cells in vitro.23,24 To assess the clinical activity of BL22, we studied patients with hairy-cell leukemia that was resistant to cladribine in a dose-escalation trial.Methods
Of the 31 patients with B-cell cancers who were enrolled in a dose-escalation trial of BL22, 16 had hairy-cell leukemia. All patients had circulating malignant cells that expressed CD22, adequate organ function, and an absence of high levels of neutralizing antibodies against BL22; all were resistant to standard chemotherapy; and all provided written, informed consent.
Between 0.2 and 4.0 mg of BL22, which was produced by the Developmental Therapeutics Program of the National Cancer Institute, was diluted in 50 ml of 0.2 percent albumin in 0.9 percent sodium chloride and administered as a 30-minute intravenous infusion every other day for a total of three doses. To diminish inflammatory adverse effects, all patients who received at least 40 μg of BL22 per kilogram of body weight also received 5 mg of infliximab, the monoclonal antibody to tumor necrosis factor α (TNF-α), per kilogram before and one week after the beginning of each cycle and 12.5 to 25.0 mg of rofecoxib, the nonsteroidal selective inhibitor of cyclooxygenase-2, per day. Patients without neutralizing antibodies who did not have progressive disease24 could be treated again after restaging at intervals of three weeks or more. After a partial response, patients could receive a total of 16 cycles of BL22, and patients who had a complete response could receive 2 additional cycles. Patients could receive higher doses of BL22 during retreatment if these doses were found to be safe in patients who received them during the initial treatment.
The disease was assessed by computed tomography, flow cytometry to detect hairy-cell-leukemia antigens, and polymerase-chain-reaction (PCR) assay of nucleated blood cells to detect immunoglobulin heavy-chain monoclonality and by histologic examination of bone marrow. The criteria for complete remission were an absence of evidence of disease in radiographic studies and an absence of tumor cells in the bone marrow and peripheral blood according to morphologic criteria, as ascertained at least four weeks after the last dose of BL22.25 The presence or absence of minimal residual disease in the biopsy specimen of bone marrow was determined microscopically by immunohistochemical analysis26 four weeks or more after the last dose of BL22 as well. Radiologic and biopsy evidence of complete remissions and determinations of whether minimal residual disease was present were independently reviewed by personnel who were unaware of the treatment status of the patients.
The maximal tolerated dose was the highest level at which dose-limiting toxic effects (at least grade 3 according to the Common Toxicity Criteria, version 2.0, with exceptions that are not considered to be dose-limiting27) occurred in none or one of six patients during the first cycle. Six patients received the maximal tolerated dose (three infusions of 40 μg per kilogram) in the first cycle. A cytotoxicity assay on Raji cells27 was used to determine plasma levels of BL22 and neutralizing antibodies. The PCR assay used to detect monoclonal B cells (hairy cells) was not sequence-specific and was performed on DNA extracted from mononuclear cells with the use of primers for framework region 3 and the junctional region of the immunoglobulin heavy-chain gene.
Results
Patients
The median age of the patients was 54 years, and the median time from diagnosis was 8 years (Table 1Table 1
Clinical Characteristics of Patients with Hairy-Cell Leukemia at the Initiation of Treatment with BL22.). Hairy cells from all patients were strongly positive for CD22, as measured by fluorescence-activated cell-sorter (FACS) analysis. Of the 16 patients, 13 had classic hairy-cell leukemia in which the cells expressed CD25, CD11c, and CD103 and had typical morphologic features. Three patients had variant disease14 in which the leukemic cells lacked CD25 or CD103 (Patients 4, 7, and 11). Before they were enrolled in the study, the patients had received a median of three courses of treatment with a purine analogue (range, one to seven); all had received and were resistant to cladribine, as defined by an inadequate response (Table 1).Dose Levels and Immunogenicity of BL22
BL22 contains a bacterial toxin that is expected to be immunogenic in humans. However, neutralizing antibodies against the toxin were generated in only 4 of the 16 patients (Patients 2, 5, 9, and 12); these antibodies were detected after cycles 4, 1, 2, and 4, respectively (Table 2Table 2
Dose Levels, Immunogenicity, and Dose-Limiting Toxic Effects of BL22 in Patients with Hairy-Cell Leukemia.). Patient 5 had a low level of neutralizing antibodies before receiving BL22 and had an anamnestic response during the first cycle. The limited immunogenicity of BL22 made possible the administration of repeated cycles.Response to BL22
Of the 16 patients, 11 had a complete remission and 2 had a partial remission. These two patients are still receiving treatment. The remaining three patients received 2 or 6 μg of BL22 per kilogram or had neutralizing antibodies before therapy was started. Residual hairy cells were always strongly positive for CD22. Patients 2 and 5 had 98.0 and 99.5 percent reductions in circulating hairy cells, respectively, but had less than 50 percent decreases in the size of abdominal masses and were not retreated because of the presence of neutralizing antibodies (Table 2). In the 13 patients with a complete or partial response, the abnormal findings on radiography disappeared. Splenomegaly resolved in all eight patients whose spleens had not been surgically removed (Table 1). As Figure 2Figure 2
Response of Patients with Pancytopenia to BL22. shows, the absolute neutrophil count, platelet count, and hemoglobin level improved after treatment. Three patients (Patients 7, 9, and 15) had iron deficiency after treatment with BL22, which may have limited the improvement in hemoglobin levels.As Table 3Table 3
Response to BL22 in Patients with Hairy-Cell Leukemia. shows, six patients had a complete remission after receiving only one cycle of BL22, whereas in five patients the remission occurred after two to nine cycles. In patients who had a response, the rapid reduction in circulating hairy cells was consistent with a direct cytotoxic effect of BL22. Levels of circulating malignant cells were measured by flow cytometry, which can detect levels of monoclonal B cells of 0.01 to 0.05 percent. In most patients there was more than a 90 percent reduction in such cells by day 3 of cycle 1 (the effect of a single dose) and more than a 99 percent reduction by day 8. Patients 9, 13, and 16 had no detectable monoclonal B cells by day 8. In Patients 4, 7, and 11, all of whom had the variant form of hairy-cell leukemia, the number of circulating hairy cells began to decrease within 24 hours after the first dose. All three patients with the variant form had never had a complete remission with chemotherapy but had a complete remission with BL22.Minimal Residual Disease
The presence of minimal residual disease in the bone marrow, as detected by immunohistochemical analysis, is associated with relatively short durations of complete remission in patients with hairy-cell leukemia.26 We assessed marrow-biopsy specimens using immunohistochemical analysis with CD20 (L26) and CD3 (Leu4) antibodies; only 1 of 11 patients in complete remission had evidence of minimal residual disease in the bone marrow (Table 3). Tests for the presence of monoclonal B cells by flow cytometry of blood were negative in 10 of the 11 patients who had complete remissions. A population of hairy cells too low to quantitate (less than 0.05 percent) was detected in one patient. PCR studies, which can detect levels of hairy cells of 0.001 to 0.1 percent, failed to detect monoclonal B cells in the peripheral blood in any of the 11 patients in complete remission.
Relapse
Of the 11 patients in complete remission, 3 (Patients 4 and 7, who had variant disease, and Patient 12, who had classic disease) relapsed 8, 12, and 7 months, respectively, after complete remission was achieved. Patient 12 had received only one cycle after entering a complete remission and was the only patient with a complete response who was found to have minimal residual disease on bone marrow biopsy. When retreated, Patients 4, 7, and 12 had another complete remission after one to three cycles; Patient 12 had had a response to retreatment.
Toxicity of BL22
BL22 caused a dose-limiting cytokine-release syndrome, defined by fever, hypotension, and myalgia or arthralgia, in Patient 5. This complication was temporally related to a secondary immune response to BL22. The level of TNF-α in this patient (112 pg per milliliter) was elevated (normal level, less than 5 pg per milliliter). To prevent the cytokine-release syndrome, Patients 8 through 16 were pretreated with rofecoxib and infliximab. In Patients 8 and 13, a serious but completely reversible hemolytic–uremic syndrome, confirmed by renal biopsy, developed after the last dose during cycle 2 (Table 2). These two patients required 6 to 10 days of plasmapheresis but not dialysis. Both patients remain in complete remission more than 11 and 16 months after treatment. Hematologic toxic effects (neutropenia, anemia, or thrombocytopenia) and decreases in the T-cell count were not observed in the other 14 patients. Less serious toxic effects included transient hypoalbuminemia, elevations in aminotransferase levels, nausea, myalgia, edema, and slight elevations in creatinine levels; all were reversible.
Discussion
We found that a recombinant immunotoxin, BL22, is active in patients with hairy-cell leukemia that is resistant to treatment with purine analogues. BL22 induced a complete remission in 11 of 16 such patients (69 percent) and a partial remission in 2. The three patients who did not have a response probably received inadequate treatment because preexisting toxin-neutralizing antibodies were present or low doses of the immunotoxin were administered. A potential confounding variable was the use of inhibitors of TNF-α in some patients to prevent the cytokine-release syndrome. Although TNF-α is considered an autocrine growth factor for hairy cells and moderate antitumor activity has been reported with inhibition of TNF-α,28 we believe it is unlikely that the use of infliximab or rofecoxib can account for our results, because four patients had already had a response before infliximab was administered. Of the 11 patients who had a complete response to BL22, 7 had never previously had a complete remission, 2 had had no response to their last course of therapy with a purine analogue, and 2 had had complete remissions lasting less than six months (Table 1). We are unaware of any other treatment, including interferon alfa, fludarabine, chlorambucil, and multiagent chemotherapy, that can produce a high rate of complete remission in patients with hairy-cell leukemia that is resistant to purine analogues. Complete remissions also occurred in all three patients with variant hairy-cell leukemia, which responds poorly to pentostatin12 and cladribine.14,29,30
Up to 50 percent of patients who have a complete response to cladribine or pentostatin still have minimal residual disease detectable by immunohistochemical analysis of bone marrow; this finding portends a decreased rate of disease-free survival.26,31,32 By contrast, minimal residual disease was present in the bone marrow of only 1 of our 11 patients who had a complete response. Despite the elimination of minimal residual disease by purine analogues, hairy cells can be detected in the marrow by sensitive PCR techniques.33,34
The low level of toxicity of BL22 made possible the administration of multiple cycles to most patients. This is potentially a major advantage over cladribine and pentostatin, both of which cause considerable myelosuppression and long-term reductions in CD4+ T cells.35,36 Although we were limited by our protocol to two cycles of consolidation therapy regardless of the presence or absence of minimal residual disease, additional cycles may be useful, particularly in patients with variant disease, if relapse is frequent after treatment with BL22. Additional follow-up of these patients and treatment of new patients will be necessary to determine whether there is a dose response.
We recently reported that the recombinant immunotoxin anti-Tac(Fv)-PE38 (LMB-2), which contains an anti-CD25 Fv fused to a truncated pseudomonas exotoxin (PE38), induced one complete remission and three partial remissions in four patients with hairy-cell leukemia that was resistant to treatment with cladribine.27,37 Like LMB-2,19 BL22 is specifically cytotoxic to primary cultures of hairy cells (data not shown), suggesting that clinical responses are due to internalization of BL22 by malignant cells. The response of hairy-cell leukemia to these new agents suggests the potential for targeting other diseases with the truncated toxin PE38. Because CD22 is expressed in all patients with hairy-cell leukemia and at higher concentrations than CD25, BL22 is the preferable recombinant immunotoxin for the treatment of this disease.
The cause of hemolytic–uremic syndrome in two of our patients, both of whom recovered fully and had complete remissions, is unknown. Fatal hemolytic–uremic syndrome was reported with the combination of the immunotoxins RFB4–deglycosylated ricin A chain (directed against CD22) and HD37–deglycosylated ricin A chain (directed against CD19) known as Combotox,38 suggesting a CD22-related mechanism.39 Since we began taking precautions to prevent renal injury, including improving hydration and avoiding the use of intravenous contrast medium immediately before treatment with BL22, we have seen no other cases of hemolytic–uremic syndrome in 63 cycles of three doses of 40 to 50 μg per kilogram. Nevertheless, the hemolytic–uremic syndrome remains a serious potential complication; in our opinion, however, the responses to BL22 justify its testing in patients with a poor prognosis.
Unlike conjugates containing the deglycosylated ricin A chain,20,21,40,41 the smaller BL22 molecule containing PE38 did not cause pulmonary edema, a serious complication of vascular-leak syndrome; this may have allowed patients with the hemolytic–uremic syndrome to recover. The absence of fatal vascular-leak syndrome with BL22 is consistent with the sensitivity of human umbilical-vein endothelial cells to the deglycosylated ricin A chain and their resistance to PE38.42,43
Supported by the National Cancer Institute.
Drs. FitzGerald and Pastan hold the partial patent rights to the invention of the truncated pseudomonas exotoxin.
We are indebted to Dr. Toby Hecht, Dr. Steve Giardina, and Daniel Coffman at the Monoclonal Antibody and Recombinant Protein Facility, Frederick, Md.; to Drs. Carolyn Laurencot, Jay Greenblatt, and Thomas Davis at the Cancer Therapy Evaluation Program, Bethesda, Md.; to Dr. David Waters at Science Applications International, Frederick, Md.; to Inger Margulies for technical assistance; to Drs. Charles Dinarello and Ellen Vitetta for helpful discussions regarding inflammatory toxic effects; to Dr. Pierre Noel for reviewing bone marrow–biopsy specimens; to Dr. Peter Choyke for reviewing radiologic results; to Lynn Sorbara and Dr. Kakushi Matsushita for performing PCR and cytokine assays; and to associate investigators Diana O'Hagan, Michelle Zancan, and Katura Fetterson for patient care and for assembling clinical data on patients who were retreated.
Source Information
From the Laboratory of Molecular Biology (R.J.K., K.B., D.J.F., I.P.), the Medicine Branch (W.H.W., M.R.), and the Laboratory of Clinical Pathology (M.S.-S.), National Cancer Institute, Bethesda, Md.
Address reprint requests to Dr. Kreitman at the National Cancer Institute, Laboratory of Molecular Biology, Bldg. 37, Rm. 4B27, 37 Convent Dr., MSC 4255, Bethesda, MD 20892, or at kreitmar@mail.nih.gov.
- References
References
1
Bouroncle BA ,Wiseman BK ,Doan CA . Leukemic reticuloendotheliosis. Blood 1958;13:609-630
Web of Science | Medline2
Bernstein L ,Newton P ,Ross RK . Epidemiology of hairy cell leukemia in Los Angeles County. Cancer Res 1990;50:3605-3609
Web of Science | Medline3
Flandrin G ,Sigaux F ,Sebahoun G ,Bouffette P . Hairy cell leukemia: clinical presentation and follow-up of 211 patients. Semin Oncol 1984;11:Suppl 2:458-471
Web of Science | Medline4
Frassoldati A ,Lamparelli T ,Federico M , et al. Hairy cell leukemia: a clinical review based on 725 cases of the Italian Cooperative Group (ICGHCL). Leuk Lymphoma 1994;13:307-316
CrossRef | Web of Science | Medline5
Bouroncle BA . The history of hairy cell leukemia: characteristics of long-term survivors. Semin Oncol 1984;11:Suppl 2:479-485
Web of Science | Medline6
Spiers ASD ,Moore D ,Cassileth PA , et al. Remissions in hairy-cell leukemia with pentostatin (2μdeoxycoformycin). N Engl J Med 1987;316:825-830
Full Text | Web of Science | Medline7
Piro LD ,Carrera CJ ,Carson DA ,Beutler E . Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine. N Engl J Med 1990;322:1117-1121
Full Text | Web of Science | Medline8
Golomb HM ,Jacobs A ,Fefer A , et al. Alpha-2 interferon therapy of hairy-cell leukemia: a multicenter study of 64 patients. J Clin Oncol 1986;4:900-905
Web of Science | Medline9
Quesada JR ,Reuben J ,Manning JT ,Hersh EM ,Gutterman JU . Alpha interferon for induction of remission in hairy-cell leukemia. N Engl J Med 1984;310:15-18
Full Text | Web of Science | Medline10
Grever M ,Kopecky K ,Foucar MK , et al. Randomized comparison of pentostatin versus interferon alfa-2a in previously untreated patients with hairy cell leukemia: an intergroup study. J Clin Oncol 1995;13:974-982
Web of Science | Medline11
Tallman MS ,Peterson LC ,Hakimian D ,Gillis S ,Polliack A . Treatment of hairy-cell leukemia: current views. Semin Hematol 1999;36:155-163
Web of Science | Medline12
Catovsky D ,Matutes E ,Talavera JG , et al. Long term results with 2μdeoxycoformycin in hairy cell leukemia. Leuk Lymphoma 1994;14:Suppl 1:109-113
Web of Science | Medline13
Saven A ,Burian C ,Koziol JA ,Piro LD . Long-term follow-up of patients with hairy cell leukemia after cladribine treatment. Blood 1998;92:1918-1926
Web of Science | Medline14
Blasinska-Morawiec M ,Robak T ,Krykowski E ,Hellmann A ,Urbanska-Rys H . Hairy cell leukemia-variant treated with 2-chlorodeoxyadenosine -- a report of three cases. Leuk Lymphoma 1997;25:381-385
Web of Science | Medline15
Vitetta ES ,Stone M ,Amlot P , et al. Phase I immunotoxin trial in patients with B-cell lymphoma. Cancer Res 1991;51:4052-4058
Web of Science | Medline16
Clark EA . CD22, a B cell-specific receptor, mediates adhesion and signal transduction. J Immunol 1993;150:4715-4718
Web of Science | Medline17
Robbins BA ,Ellison DJ ,Spinosa JC , et al. Diagnostic application of two-color flow cytometry in 161 cases of hairy cell leukemia. Blood 1993;82:1277-1287
Web of Science | Medline18
Cordone I ,Annino L ,Masi S , et al. Diagnostic relevance of peripheral blood immunocytochemistry in hairy cell leukaemia. J Clin Pathol 1995;48:955-960
CrossRef | Web of Science | Medline19
Robbins DH ,Margulies I ,Stetler-Stevenson M ,Kreitman RJ . Hairy cell leukemia, a B-cell neoplasm that is particularly sensitive to the cytotoxic effect of anti-Tac(Fv)-PE38 (LMB-2). Clin Cancer Res 2000;6:693-700
Web of Science | Medline20
Amlot PL ,Stone MJ ,Cunningham D , et al. A phase I study of an anti-CD22-deglycosylated ricin A chain immunotoxin in the treatment of B-cell lymphomas resistant to conventional therapy. Blood 1993;82:2624-2633
Web of Science | Medline21
Sausville EA ,Headlee D ,Stetler-Stevenson M , et al. Continuous infusion of the anti-CD22 immunotoxin IgG-RFB4-SMPT-dgA in patients with B-cell lymphoma: a phase I study. Blood 1995;85:3457-3465
Web of Science | Medline22
Kreitman RJ . Immunotoxins in cancer therapy. Curr Opin Immunol 1999;11:570-578
CrossRef | Web of Science | Medline23
Kreitman RJ ,Wang QC ,FitzGerald DJP ,Pastan I . Complete regression of human B-cell lymphoma xenografts in mice treated with recombinant anti-CD22 immunotoxin RFB4(dsFv)-PE38 at doses tolerated by cynomolgus monkeys. Int J Cancer 1999;81:148-155
CrossRef | Web of Science | Medline24
Kreitman RJ ,Margulies I ,Stetler-Stevenson M ,Wang QC ,FitzGerald DJP ,Pastan I . Cytotoxic activity of disulfide-stabilized recombinant immunotoxin RFB4(dsFv)-PE38 (BL22) toward fresh malignant cells from patients with B-cell leukemia. Clin Cancer Res 2000;6:1467-148725
Cheson BD ,Horning SJ ,Coiffier B , et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. J Clin Oncol 1999;17:1244-1244[Erratum, J Clin Oncol 2000;18:2351.]
Web of Science | Medline26
Tallman MS ,Hakimian D ,Kopecky KJ , et al. Minimal residual disease in patients with hairy cell leukemia in complete remission treated with 2-chlorodeoxyadenosine or 2-deoxycoformycin and prediction of early relapse. Clin Cancer Res 1999;5:1665-1670
Web of Science | Medline27
Kreitman RJ ,Wilson WH ,White JD , et al. Phase I trial of recombinant immunotoxin Anti-Tac(Fv)-PE38 (LMB-2) in patients with hematologic malignancies. J Clin Oncol 2000;18:1622-1636
Web of Science | Medline28
Huang D ,Reittie JE ,Stephens S ,Hoffbrand AV ,Brenner MK . Effects of anti-TNF monoclonal antibody infusion in patients with hairy cell leukaemia. Br J Haematol 1992;81:231-234
CrossRef | Web of Science | Medline29
Rak K ,Kiss A ,Posan E ,Telek B ,Szakall S ,Ujj G . Hairy cell leukemia variant treated with success by 2-chlorodeoxyadenosine. Blood 1998;92:Suppl 1:282b-282b abstract.
Web of Science30
Tetreault S ,Saven A . Treatment of hairy cell leukemia-variant (HCL-V) with cladribine. Blood 1998;92:Suppl 1:283b-283b abstract.
Web of Science31
Ellison DJ ,Sharpe RW ,Robbins BA , et al. Immunomorphologic analysis of bone marrow biopsies after treatment with 2-chlorodeoxyadenosine for hairy cell leukemia. Blood 1994;84:4310-4315
Web of Science | Medline32
Wheaton S ,Tallman MS ,Hakimian D ,Peterson L . Minimal residual disease may predict bone marrow relapse in patients with hairy cell leukemia treated with 2-chlorodeoxyadenosine. Blood 1996;87:1556-1560
Web of Science | Medline33
Filleul B ,Delannoy A ,Ferrant A , et al. A single course of 2-chlorodeoxyadenosine does not eradicate leukemic cells in hairy cell leukemia patients in complete remission. Leukemia 1994;8:1153-1156
Web of Science | Medline34
Carbone A ,Reato G ,Di Celle PF ,Lauria F ,Foa R . Disease eradication in hairy cell leukemia patients treated with 2-chlorodeoxyadenosine. Leukemia 1994;8:2019-2020
Web of Science | Medline35
Seymour JF ,Kurzrock R ,Freireich EJ ,Estey EH . 2-Chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia. Blood 1994;83:2906-2911
Web of Science | Medline36
Seymour JF ,Talpaz M ,Kurzrock R . Response duration and recovery of CD4+ lymphocytes following deoxycoformycin in interferon-alpha-resistant hairy cell leukemia: 7-year follow-up. Leukemia 1997;11:42-47
CrossRef | Web of Science | Medline37
Kreitman RJ ,Wilson WH ,Robbins D , et al. Responses in refractory hairy cell leukemia to a recombinant immunotoxin. Blood 1999;94:3340-3348
Web of Science | Medline38
Messmann RA ,Vitetta ES ,Headlee D , et al. A phase I study of combination therapy with immunotoxins IgG-HD37-deglycosylated ricin A chain (dgA) and IgG-RFB4-dgA (Combotox) in patients with refractory CD19(+), CD22(+) B cell lymphoma. Clin Cancer Res 2000;6:1302-1313
Web of Science | Medline39
Schwager I ,Jungi TW . Effect of human recombinant cytokines on the induction of macrophage procoagulant activity. Blood 1994;83:152-160
Web of Science | Medline40
Conry RM ,Khazaeli MB ,Saleh MN , et al. Phase I trial of an anti-CD19 deglycosylated ricin A chain immunotoxin in non-Hodgkin's lymphoma: effect of an intensive schedule of administration. J Immunother Emphasis Tumor Immunol 1995;18:231-241
CrossRef | Web of Science | Medline41
Stone MJ ,Sausville EA ,Fay JW , et al. A phase I study of bolus versus continuous infusion of the anti-CD19 immunotoxin, IgG-HD37-dgA, in patients with B-cell lymphoma. Blood 1996;88:1188-1197
Web of Science | Medline42
Baluna R ,Rizo J ,Gordon BE ,Ghetie V ,Vitetta ES . Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome. Proc Natl Acad Sci U S A 1999;96:3957-3962
CrossRef | Web of Science | Medline43
Kuan C-T ,Pai LH ,Pastan I . Immunotoxins containing Pseudomonas exotoxin that target LeY damage human endothelial cells in an antibody-specific mode: relevance to vascular leak syndrome. Clin Cancer Res 1995;1:1589-1594
Web of Science | Medline
- Citing Articles (172)
Citing Articles
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Rahul R. Naik, Alan Saven. (2012) My Treatment Approach to Hairy Cell Leukemia. Mayo Clinic Proceedings 87:1, 67-76
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CrossRef6
C. Kellner, W.K. Bleeker, J.J. Lammerts van Bueren, M. Staudinger, K. Klausz, S. Derer, P. Glorius, A. Muskulus, B.E.C.G. de Goeij, J.G.J. van de Winkel, P.W.H.I. Parren, T. Valerius, M. Gramatzki, M. Peipp. (2011) Human kappa light chain targeted Pseudomonas exotoxin A — identifying human antibodies and Fab fragments with favorable characteristics for antibody–drug conjugate development. Journal of Immunological Methods 371:1-2, 122-133
CrossRef7
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CrossRef8
Ira Pastan, Masanori Onda, John Weldon, David Fitzgerald, Robert Kreitman. (2011) Immunotoxins with decreased immunogenicity and improved activity. Leukemia & Lymphoma 52:S2, 87-90
CrossRef9
Evgeny Arons, Robert J. Kreitman. (2011) Molecular variant of hairy cell leukemia with poor prognosis. Leukemia & Lymphoma 52:S2, 99-102
CrossRef10
Yingyun Cai, Edward A. Berger. (2011) An immunotoxin targeting the gH glycoprotein of KSHV for selective killing of cells in the lytic phase of infection. Antiviral Research 90:3, 143-150
CrossRef11
Robert J. Kreitman, Evgeny Arons, Maryalice Stetler-Stevenson, David J. P. Fitzgerald, Wyndham H. Wilson, Ira Pastan. (2011) Recombinant immunotoxins and other therapies for relapsed/refractory hairy cell leukemia. Leukemia & Lymphoma 52:S2, 82-86
CrossRef12
Harvey M. Golomb. (2011) Fifty years of hairy cell leukemia treatments. Leukemia & Lymphoma 52:S2, 3-5
CrossRef13
Robert J. Kreitman, Evgeny Arons, Maryalice Stetler-stevenson, Kenneth B. Miller. (2011) Response of hairy cell leukemia to bendamustine. Leukemia & Lymphoma 52:6, 1153-1156
CrossRef14
E. Arons, L. Roth, J. Sapolsky, T. Suntum, M. Stetler-Stevenson, R. J. Kreitman. (2011) Evidence of canonical somatic hypermutation in hairy cell leukemia. Blood 117:18, 4844-4851
CrossRef15
Haya Lorberboum-Galski. (2011) Human toxin-based recombinant immunotoxins/chimeric proteins as a drug delivery system for targeted treatment of human diseases. Expert Opinion on Drug Delivery 8:5, 605-621
CrossRef16
Roberta Traini, Robert J Kreitman. (2011) Renal Excretion of Recombinant Immunotoxins Containing Pseudomonas Exotoxin. Bioconjugate Chemistry 22:4, 736-740
CrossRef17
Kevin T. Kim, Darren S. Sigal, Alan Saven. 2011. Hairy Cell Leukemia. , 253-265.
CrossRef18
Monique A. Hartley-Brown, Lubomir Sokol. 2011. Molecular Biology of Chronic Lymphoproliferative Disorders. , 191-210.
CrossRef19
M. Onda, R. Beers, L. Xiang, B. Lee, J. E. Weldon, R. J. Kreitman, I. Pastan. (2011) Recombinant immunotoxin against B-cell malignancies with no immunogenicity in mice by removal of B-cell epitopes. Proceedings of the National Academy of Sciences 108:14, 5742-5747
CrossRef20
Richard R. Furman, Michael L. Grossbard, Jeffrey L. Johnson, Andrew L. Pecora, Peter A. Cassileth, Sin-Ho Jung, Bruce A. Peterson, Lee M. Nadler, Arnold Freedman, Ruthee-Lu Bayer, Nancy L. Bartlett, David D. Hurd, Bruce D. Cheson, For The Cancer Leukemia Group B And. (2011) A phase III study of anti-B4-blocked ricin as adjuvant therapy post-autologous bone marrow transplant: CALGB 9254. Leukemia & Lymphoma 52:4, 587-596
CrossRef21
A D Ricart. (2011) Immunoconjugates Against Solid Tumors: Mind the Gap. Clinical Pharmacology & Therapeutics 89:4, 513-523
CrossRef22
Lorin K Roskos, Amy Schneider, Inna Vainshtein, Martin Schwickart, Rozanne Lee, Hong Lu, Raffaella Faggioni, Meina Liang. (2011) PK–PD modeling of protein drugs: implications in assay development. Bioanalysis 3:6, 659-675
CrossRef23
Tadeusz Robak. (2011) Hairy-cell leukemia variant: Recent view on diagnosis, biology and treatment. Cancer Treatment Reviews 37:1, 3-10
CrossRef24
Hsiao-Wen Kao, Po Dunn, Ming-Chung Kuo, Lee-Yung Shih, Tung-Liang Lin, Jin-Hou Wu, Tzung-Chih Tang, Hung Chang, Hong-Cheng Wu, Yu-Shin Hung. (2011) Classical Hairy Cell Leukemia and Its Variant: A 17-Year Retrospective Survey in Taiwan Chinese. Acta Haematologica 126:3, 186-193
CrossRef25
Kristin Loomis, Kathleen McNeeley, Ravi V. Bellamkonda. (2011) Nanoparticles with targeting, triggered release, and imaging functionality for cancer applications. Soft Matter 7:3, 839
CrossRef26
F. Pandolfi, R. Cianci, D. Pagliari, F. Casciano, C. Bagalà, A. Astone, R. Landolfi, C. Barone. (2011) The Immune Response to Tumors as a Tool toward Immunotherapy. Clinical and Developmental Immunology 2011, 1-12
CrossRef27
Gregory S Vosganian, Darren S Sigal, Alan Saven. (2010) Hairy cell leukemia: current therapies and future directions. Expert Review of Hematology 3:6, 679-683
CrossRef28
Ali ElBakri, Paul N. Nelson, Raed O. Abu Odeh. (2010) The state of antibody therapy. Human Immunology 71:12, 1243-1250
CrossRef29
Eric Schafer, Donald Small. 2010. Non-Cytogenetic Markers and their Impact on Prognosis. , 56-76.
CrossRef30
Farhad Ravandi. 2010. Hairy Cell Leukemia. , 339-347.
CrossRef31
Ashima K. Sharma, David FitzGerald. (2010) Pseudomonas exotoxin kills Drosophila S2 cells via apoptosis. Toxicon 56:6, 1025-1034
CrossRef32
Geert-Jan Boons. (2010) Liposomes modified by carbohydrate ligands can target B cells for the treatment of B-cell lymphomas. Expert Review of Vaccines 9:11, 1251-1256
CrossRef33
Pier Luigi Zinzani, Cinzia Pellegrini, Vittorio Stefoni, Enrico Derenzini, Letizia Gandolfi, Alessandro Broccoli, Lisa Argnani, Federica Quirini, Stefano Pileri, Michele Baccarani. (2010) Hairy cell leukemia. Cancer 116:20, 4788-4792
CrossRef34
Francis Mussai, Dario Campana, Deepa Bhojwani, Maryalice Stetler-Stevenson, Seth M. Steinberg, Alan S. Wayne, Ira Pastan. (2010) Cytotoxicity of the anti-CD22 immunotoxin HA22 (CAT-8015) against paediatric acute lymphoblastic leukaemia. British Journal of Haematology 150:3, 352-358
CrossRef35
Todd L. Rosenblat, Joseph G. Jurcic. 2010. Radioimmunotherapy of Acute Myeloid Leukemia. , 219-239.
CrossRef36
Philipp Wolf, Ursula Elsässer-Beile. 2010. Pseudomonas Exotoxin A-Based Immunotoxins for Targeted Cancer Therapy. , 269-288.
CrossRef37
W. C. Chen, G. C. Completo, D. S. Sigal, P. R. Crocker, A. Saven, J. C. Paulson. (2010) In vivo targeting of B-cell lymphoma with glycan ligands of CD22. Blood 115:23, 4778-4786
CrossRef38
Robert Sarnovsky, Tara Tendler, Matheusz Makowski, Maureen Kiley, Antonella Antignani, Roberta Traini, Jingli Zhang, Raffit Hassan, David J. FitzGerald. (2010) Initial characterization of an immunotoxin constructed from domains II and III of cholera exotoxin. Cancer Immunology, Immunotherapy 59:5, 737-746
CrossRef39
Johanna K. Hansen, John E. Weldon, Laiman Xiang, Richard Beers, Masanori Onda, Ira Pastan. (2010) A Recombinant Immunotoxin Targeting CD22 With Low Immunogenicity, Low Nonspecific Toxicity, and High Antitumor Activity in Mice. Journal of Immunotherapy 33:3, 297-304
CrossRef40
Jennifer G. Brown, Joycelyn Entwistle, Nick Glover, Glen C. Macdonald. 2010. Preclinical Safety Evaluation of Immunotoxins. .
CrossRef41
Andrew J.T. George. 2010. Monoclonal Antibody Therapy. .
CrossRef42
Christoph Stein, Christian Kellner, Markus Kügler, Nina Reiff, Kristin Mentz, Michael Schwenkert, Bernhard Stockmeyer, Andreas Mackensen, Georg H. Fey. (2010) Novel conjugates of single-chain Fv antibody fragments specific for stem cell antigen CD123 mediate potent death of acute myeloid leukaemia cells. British Journal of Haematology 148:6, 879-889
CrossRef43
Christian Bogner, Tobias Dechow, Ingo Ringshausen, Michaela Wagner, Madlen Oelsner, Gloria Lutzny, Thomas Licht, Christian Peschel, Ira Pastan, Robert J Kreitman, Thomas Decker. (2010) Immunotoxin BL22 induces apoptosis in mantle cell lymphoma (MCL) cells dependent on Bcl-2 expression. British Journal of Haematology 148:1, 99-109
CrossRef44
Hossein Borghaei, Mitchell R. Smith, Kerry S. Campbell. (2009) Immunotherapy of cancer. European Journal of Pharmacology 625:1-3, 41-54
CrossRef45
Mayra Tejuca, Gregor Anderluh, Mauro Dalla Serra. (2009) Sea anemone cytolysins as toxic components of immunotoxins. Toxicon 54:8, 1206-1214
CrossRef46
Thomas S. Lin, Wendy Stock, Huiping Xu, Mitch A. Phelps, Margaret S. Lucas, Sara K. Guster, Bruce R. Briggs, Carolyn Cheney, Pierluigi Porcu, Ian W. Flinn, Michael R. Grever, James T. Dalton, John C. Byrd. (2009) A phase I/II dose escalation study of apolizumab (Hu1D10) using a stepped-up dosing schedule in patients with chronic lymphocytic leukemia and acute leukemia. Leukemia & Lymphoma 50:12, 1958-1963
CrossRef47
E. Arons, T. Suntum, M. Stetler-Stevenson, R. J. Kreitman. (2009) VH4-34+ hairy cell leukemia, a new variant with poor prognosis despite standard therapy. Blood 114:21, 4687-4695
CrossRef48
Farhad Ravandi. (2009) Hairy Cell Leukemia. Clinical Lymphoma, Myeloma & Leukemia 9:0, S254-S259
CrossRef49
John C. Morris, Thomas A. Waldmann. (2009) Antibody-based therapy of leukaemia. Expert Reviews in Molecular Medicine 11,
CrossRef50
Mary K. O’Reilly, James C. Paulson. (2009) Siglecs as targets for therapy in immune-cell-mediated disease. Trends in Pharmacological Sciences 30:5, 240-248
CrossRef51
J. E. Weldon, L. Xiang, O. Chertov, I. Margulies, R. J. Kreitman, D. J. FitzGerald, I. Pastan. (2009) A protease-resistant immunotoxin against CD22 with greatly increased activity against CLL and diminished animal toxicity. Blood 113:16, 3792-3800
CrossRef52
Patrick Brown, Steven P Hunger, Franklin O Smith, William L Carroll, Gregory H Reaman. (2009) Novel targeted drug therapies for the treatment of childhood acute leukemia. Expert Review of Hematology 2:2, 145-158
CrossRef53
Philipp Wolf, Ursula Elsässer-Beile. (2009) Pseudomonas exotoxin A: From virulence factor to anti-cancer agent. International Journal of Medical Microbiology 299:3, 161-176
CrossRef54
Louis M Weiner, Madhav V Dhodapkar, Soldano Ferrone. (2009) Monoclonal antibodies for cancer immunotherapy. The Lancet 373:9668, 1033-1040
CrossRef55
Thomas Schirrmann, Jürgen Krauss, Michaela AE Arndt, Susanna M Rybak, Stefan Dübel. (2009) Targeted therapeutic RNases (ImmunoRNases). Expert Opinion on Biological Therapy 9:1, 79-95
CrossRef56
Robert J. Kreitman, David J. P. Fitzgerald, Ira Pastan. (2009) Approach to the patient after relapse of hairy cell leukemia. Leukemia & Lymphoma 50:s1, 32-37
CrossRef57
Robert J. Kreitman. (2009) Recombinant Immunotoxins Containing Truncated Bacterial Toxins for the Treatment of Hematologic Malignancies. BioDrugs 23:1, 1-13
CrossRef58
Martin S. Tallman, Aaron Polliack. (2009) Historical aspects and milestones in the development of effective treatment for hairy cell leukemia. Leukemia & Lymphoma 50:s1, 2-7
CrossRef59
Yasuhiro ABE. (2009) Development of Novel DDS Technologies for Optimized Protein Therapy by Creating Functional Mutant Proteins with Antagonistic Activity. YAKUGAKU ZASSHI 129:8, 933-939
CrossRef60
Tadeusz Robak. (2008) Treatment of chronic lymphoid leukemias with monoclonal antibodies: current place and perspectives. Drug Development Research 69:7, 373-387
CrossRef61
Matthew D. Marsden, Jie Xu, Dean Hamer, Jerome A. Zack. (2008) Short Communication: Activating Stimuli Enhance Immunotoxin-Mediated Killing of HIV-Infected Macrophages. AIDS Research and Human Retroviruses 24:11, 1399-1404
CrossRef62
K. Matsushita, I. Margulies, M. Onda, S. Nagata, M. Stetler-Stevenson, R. J. Kreitman. (2008) Soluble CD22 as a tumor marker for hairy cell leukemia. Blood 112:6, 2272-2277
CrossRef63
Evgeny Arons, Tara Suntum, Inger Margulies, Constance Yuan, Maryalice Stetler-Stevenson, Robert J. Kreitman. (2008) PRAME expression in hairy cell leukemia. Leukemia Research 32:9, 1400-1406
CrossRef64
M. Onda, R. Beers, L. Xiang, S. Nagata, Q.-c. Wang, I. Pastan. (2008) An immunotoxin with greatly reduced immunogenicity by identification and removal of B cell epitopes. Proceedings of the National Academy of Sciences 105:32, 11311-11316
CrossRef65
Mahendra P Deonarain. (2008) Recombinant antibodies for cancer therapy. Expert Opinion on Biological Therapy 8:8, 1123-1141
CrossRef66
Mitchell R. Smith. (2008) Antibodies and Hematologic Malignancies. The Cancer Journal 14:3, 184-190
CrossRef67
Michael Schwenkert, Katrin Birkholz, Michael Schwemmlein, Christian Kellner, Markus Kügler, Matthias Peipp, Dirk M. Nettelbeck, Beatrice Schuler-Thurner, Niels Schaft, Jan Dörrie, Soldano Ferrone, Eckhart Kämpgen, Georg H. Fey. (2008) A single chain immunotoxin, targeting the melanoma-associated chondroitin sulfate proteoglycan, is a potent inducer of apoptosis in cultured human melanoma cells. Melanoma Research 18:2, 73-84
CrossRef68
Tadeusz Robak. (2008) Emerging drugs for rarer chronic lymphoid leukemias. Expert Opinion on Emerging Drugs 13:1, 95-118
CrossRef69
Michael J Brumlik, Benjamin J Daniel, Reinhard Waehler, David T Curiel, Francis J Giles, Tyler J Curiel. (2008) Trends in immunoconjugate and ligand-receptor based targeting development for cancer therapy. Expert Opinion on Drug Delivery 5:1, 87-103
CrossRef70
Hidenobu Ochiai, Gary E. Archer, James E. Herndon, Chien-Tsun Kuan, Duane A. Mitchell, Darell D. Bigner, Ira H. Pastan, John H. Sampson. (2008) EGFRvIII-targeted immunotoxin induces antitumor immunity that is inhibited in the absence of CD4+ and CD8+ T cells. Cancer Immunology, Immunotherapy 57:1, 115-121
CrossRef71
X. Du, S. Nagata, T. Ise, M. Stetler-Stevenson, I. Pastan. (2008) FCRL1 on chronic lymphocytic leukemia, hairy cell leukemia, and B-cell non-Hodgkin lymphoma as a target of immunotoxins. Blood 111:1, 338-343
CrossRef72
David Filpula, Hong Zhao. (2008) Releasable PEGylation of proteins with customized linkers. Advanced Drug Delivery Reviews 60:1, 29-49
CrossRef73
Monica Else, Nnenna Osuji, Francesco Forconi, Claire Dearden, Ilaria Del Giudice, Estella Matutes, Andrew Wotherspoon, Francesco Lauria, Daniel Catovsky. (2007) The role of rituximab in combination with pentostatin or cladribine for the treatment of recurrent/refractory hairy cell leukemia. Cancer 110:10, 2240-2247
CrossRef74
Y. Zhang, L. Xiang, R. Hassan, I. Pastan. (2007) Immunotoxin and Taxol synergy results from a decrease in shed mesothelin levels in the extracellular space of tumors. Proceedings of the National Academy of Sciences 104:43, 17099-17104
CrossRef75
Susan E. Becker. (2007) The Disease With Hope: Hairy Cell Leukemia. Clinical Journal of Oncology Nursing 11:5, 731-735
CrossRef76
Louis M. Weiner. (2007) Building better magic bullets — improving unconjugated monoclonal antibody therapy for cancer. Nature Reviews Cancer 7:9, 701-706
CrossRef77
Louis M. Weiner. (2007) Emerging concepts in monocloal antibody therapy. European Journal of Cancer Supplements 5:5, 442-443
CrossRef78
Xing Du, Mitchell Ho, Ira Pastan. (2007) New Immunotoxins Targeting CD123, a Stem Cell Antigen on Acute Myeloid Leukemia Cells. Journal of Immunotherapy 30:6, 607-613
CrossRef79
Z R Yang, H F Wang, J Zhao, Y Y Peng, J Wang, B-A Guinn, L Q Huang. (2007) Recent developments in the use of adenoviruses and immunotoxins in cancer gene therapy. Cancer Gene Therapy 14:7, 599-615
CrossRef80
Ronan Swords, Francis Giles. (2007) Hairy cell leukemia. Medical Oncology 24:1, 7-15
CrossRef81
Hossein Borghaei, R. Katherine Alpaugh, Patricia Bernardo, Irma E. Palazzo, Janice P. Dutcher, Usha Venkatraj, William C. Wood, Lori Goldstein, Louis M. Weiner. (2007) Induction of Adaptive Anti-HER2/neu Immune Responses in a Phase 1B/2 Trial of 2B1 Bispecific Murine Monoclonal Antibody in Metastatic Breast Cancer (E3194): A Trial Coordinated by the Eastern Cooperative Oncology Group. Journal of Immunotherapy 30:4, 455-467
CrossRef82
Yiwen Li, Zhenping Zhu. (2007) Monoclonal antibody-based therapeutics for leukemia. Expert Opinion on Biological Therapy 7:3, 319-330
CrossRef83
Christopher F Nicodemus, L Mary Smith, Birgit C Schultes. (2007) Role of monoclonal antibodies in tumor-specific immunity. Expert Opinion on Biological Therapy 7:3, 331-343
CrossRef84
Ira Pastan, Raffit Hassan, David J. FitzGerald, Robert J. Kreitman. (2007) Immunotoxin Treatment of Cancer *. Annual Review of Medicine 58:1, 221-237
CrossRef85
Robert J. Kreitman, Ira Pastan. (2006) BL22 and lymphoid malignancies. Best Practice & Research Clinical Haematology 19:4, 685-699
CrossRef86
Robert J. Kreitman, Ira Pastan. (2006) Immunotoxins in the Treatment of Refractory Hairy Cell Leukemia. Hematology/Oncology Clinics of North America 20:5, 1137-1151
CrossRef87
Deborah A. Thomas, Farhad Ravandi, Hagop Kantarjian. (2006) Monoclonal Antibody Therapy for Hairy Cell Leukemia. Hematology/Oncology Clinics of North America 20:5, 1125-1136
CrossRef88
Adi Gidron, Martin S. Tallman. (2006) Hairy Cell Leukemia: Towards a Curative Strategy. Hematology/Oncology Clinics of North America 20:5, 1153-1162
CrossRef89
Claire Dearden, Monica Else. (2006) Hairy cell leukemia. Current Oncology Reports 8:5, 337-342
CrossRef90
Rajesh Belani, Alan Saven. (2006) Cladribine in Hairy Cell Leukemia. Hematology/Oncology Clinics of North America 20:5, 1109-1123
CrossRef91
Yoram Reiter, Avital Lev. 2006. Immunotoxins and Recombinant Immunotoxins in Cancer Therapy. .
CrossRef92
Y Jia, H Li, W Chen, M Li, M Lv, P Feng, H Hu, L Zhang. (2006) Prevention of murine experimental autoimmune encephalomyelitis by in vivo expression of a novel recombinant immunotoxin DT390-RANTES. Gene Therapy 13:18, 1351-1359
CrossRef93
Yingjuan Lu, Jun Yang, Emanuela Sega. (2006) Issues related to targeted delivery of proteins and peptides. The AAPS Journal 8:3, E466-E478
CrossRef94
Robert J. Kreitman. (2006) Immunotoxins for targeted cancer therapy. The AAPS Journal 8:3, E532-E551
CrossRef95
Evgeny Arons, Lynn Sorbara, Mark Raffeld, Maryalice Stetler-Stevenson, Seth M. Steinberg, David J. Liewehr, Ira Pastan, Robert J. Kreitman. (2006) Characterization of T-cell repertoire in hairy cell leukemia patients before and after recombinant immunotoxin BL22 therapy. Cancer Immunology, Immunotherapy 55:9, 1100-1110
CrossRef96
Tadeusz Robak. (2006) Current treatment options in hairy cell leukemia and hairy cell leukemia variant. Cancer Treatment Reviews 32:5, 365-376
CrossRef97
Ira Pastan, Raffit Hassan, David J. FitzGerald, Robert J. Kreitman. (2006) Immunotoxin therapy of cancer. Nature Reviews Cancer 6:7, 559-565
CrossRef98
C Kimchi-Sarfaty, W D Vieira, D Dodds, A Sherman, R J Kreitman, S Shinar, M M Gottesman. (2006) SV40 Pseudovirion gene delivery of a toxin to treat human adenocarcinomas in mice. Cancer Gene Therapy 13:7, 648-657
CrossRef99
Tomoko Ise, Robert J. Kreitman, Ira Pastan, Satoshi Nagata. (2006) Sandwich ELISAs for soluble immunoglobulin superfamily receptor translocation-associated 2 (IRTA2)/FcRH5 (CD307) proteins in human sera. Clinical Chemistry and Laboratory Medicine 44:5, 594-602
CrossRef100
Michael Schwemmlein, Matthias Peipp, Karin Barbin, Domenica Saul, Bernhard Stockmeyer, Roland Repp, Josef Birkmann, Fuat Oduncu, Bertold Emmerich, Georg H. Fey. (2006) A CD33-specific single-chain immunotoxin mediates potent apoptosis of cultured human myeloid leukaemia cells. British Journal of Haematology 133:2, 141-151
CrossRef101
Yohei Mukai, Toshiki Sugita, Tomoko Yamato, Natsue Yamanada, Hiroko Shibata, Sunao Imai, Yasuhiro Abe, Kazuya Nagano, Tetsuya Nomura, Yasuo Tsutsumi, Haruhiko Kamada, Shinsaku Nakagawa, Shin-ichi Tsunoda. (2006) Creation of Novel Protein Transduction Domain (PTD) Mutants by a Phage Display-Based High-Throughput Screening System. Biological & Pharmaceutical Bulletin 29:8, 1570-1574
CrossRef102
Adi Gidron, Martin S. Tallman. (2006) 2-CdA in the treatment of hairy cell leukemia: a review of long-term follow-up. Leukemia & Lymphoma 47:11, 2301-2307
CrossRef103
Sun-Long Cheng, Rosa Huang Liu, Jin-Nan Sheu, Shui-Tein Chen, Supachok Sinchaikul, Gregory Jiazer Tsay. (2006) Toxicogenomics of Kojic Acid on Gene Expression Profiling of A375 Human Malignant Melanoma Cells. Biological & Pharmaceutical Bulletin 29:4, 655-669
CrossRef104
Monica Else, Rosa Ruchlemer, Nnenna Osuji, Ilaria Del Giudice, Estella Matutes, Anthony Woodman, Andrew Wotherspoon, John Swansbury, Claire Dearden, Daniel Catovsky. (2005) Long remissions in hairy cell leukemia with purine analogs. Cancer 104:11, 2442-2448
CrossRef105
Lucas Wong, Dick Y. Suh, Arthur E. Frankel. (2005) Toxin Conjugate Therapy of Cancer. Seminars in Oncology 32:6, 591-595
CrossRef106
F. Ravandi, S. O'Brien. (2005) Chronic Lymphoid Leukemias Other Than Chronic Lymphocytic Leukemia: Diagnosis and Treatment. Mayo Clinic Proceedings 80:12, 1660-1674
CrossRef107
Gregory P Adams, Louis M Weiner. (2005) Monoclonal antibody therapy of cancer. Nature Biotechnology 23:9, 1147-1157
CrossRef108
Maureen O. Ripple, Sahana Kalmadi, Alan Eastman. (2005) Inhibition of Either Phosphatidylinositol 3-kinase/Akt or the Mitogen/Extracellular-regulated Kinase, MEK/ERK, Signaling Pathways Suppress Growth of Breast Cancer Cell Lines, but MEK/ERK Signaling is Critical for Cell Survival. Breast Cancer Research and Treatment 93:2, 177-188
CrossRef109
L Johannes, D Decaudin. (2005) Protein toxins: intracellular trafficking for targeted therapy. Gene Therapy 12:18, 1360-1368
CrossRef110
Farhad Ravandi, Susan O’Brien. (2005) Infections associated with purine analogs and monoclonal antibodies. Blood Reviews 19:5, 253-273
CrossRef111
Jürgen Krauss, Michaela A.E. Arndt, Bang K. Vu, Dianne L. Newton, Siegfried Seeber, Susanna M. Rybak. (2005) Efficient killing of CD22+ tumor cells by a humanized diabody–RNase fusion protein. Biochemical and Biophysical Research Communications 331:2, 595-602
CrossRef112
S. Nagata, T. Ise, M. Onda, K. Nakamura, M. Ho, A. Raubitschek, I. H. Pastan. (2005) Cell membrane-specific epitopes on CD30: Potentially superior targets for immunotherapy. Proceedings of the National Academy of Sciences 102:22, 7946-7951
CrossRef113
Michaela A. E Arndt, J??rgen Krauss, Bang K Vu, Dianne L Newton, Susanna M Rybak. (2005) A Dimeric Angiogenin Immunofusion Protein Mediates Selective Toxicity Toward CD22+ Tumor Cells. Journal of Immunotherapy 28:3, 245-251
CrossRef114
Partha S. Chowdhury, Herren Wu. (2005) Tailor-made antibody therapeutics. Methods 36:1, 11-24
CrossRef115
Federica Cavallo, Claudia Curcio, Guido Forni. (2005) Immunotherapy and immunoprevention of cancer: where do we stand?. Expert Opinion on Biological Therapy 5:5, 717-726
CrossRef116
Jurgen Krauss, Michaela A.E. Arndt, Bang K. Vu, Dianne L. Newton, Susanna M. Rybak. (2005) Targeting malignant B-cell lymphoma with a humanized anti-CD22 scFv-angiogenin immunoenzyme. British Journal of Haematology 128:5, 602-609
CrossRef117
Martin S. Tallman, Anaadriana Zakarija. (2005) Hairy cell leukemia: survival and relapse. Transfusion and Apheresis Science 32:1, 99-103
CrossRef118
John F. DiJoseph, Andrew Popplewell, Simon Tickle, Heather Ladyman, Alastair Lawson, Arthur Kunz, Kiran Khandke, Douglas C. Armellino, Erwin R. Boghaert, Philip R. Hamann, Karen Zinkewich-Peotti, Sue Stephens, Neil Weir, Nitin K. Damle. (2005) Antibody-targeted chemotherapy of B-cell lymphoma using calicheamicin conjugated to murine or humanized antibody against CD22. Cancer Immunology, Immunotherapy 54:1, 11-24
CrossRef119
S Narat, J Gandla, A Dogan, A Mehta. (2005) Successful treatment of hairy cell leukemia variant with rituximab. Leukemia & Lymphoma 46:8, 1229-1232
CrossRef120
Giulia Cervetti, Sara Galimberti, Francesca Andreazzoli, Rita Fazzi, Nadia Cecconi, Francesco Caracciolo, Mario Petrini. (2004) Rituximab as treatment for minimal residual disease in hairy cell leukaemia. European Journal of Haematology 73:6, 412-417
CrossRef121
Natalya Greyz, Alan Saven. (2004) Cladribine: from the bench to the bedside – focus on hairy cell leukemia. Expert Review of Anticancer Therapy 4:5, 745-757
CrossRef122
Satoshi Nagata, Yoshito Numata, Masanori Onda, Tomoko Ise, Yoonsoo Hahn, Byungkook Lee, Ira Pastan. (2004) Rapid grouping of monoclonal antibodies based on their topographical epitopes by a label-free competitive immunoassay. Journal of Immunological Methods 292:1-2, 141-155
CrossRef123
Yasuo Yoshioka, Yasuo Tsutsumi, Yohei Mukai, Hiroko Shibata, Takayuki Okamoto, Yoshihisa Kaneda, Shin-ichi Tsunoda, Haruhiko Kamada, Keiichi Koizumi, Yoko Yamamoto, Yu Mu, Hiroshi Kodaira, Keiko Sato-Kamada, Shinsaku Nakagawa, Tadanori Mayumi. (2004) Effective accumulation of poly(vinylpyrrolidone-co-vinyl laurate) into the spleen. Journal of Biomedical Materials Research 70A:2, 219-223
CrossRef124
Richard R. Furman, Morton Coleman, John P. Leonard. (2004) Epratuzumab in non-hodgkin’ lymphomas. Current Treatment Options in Oncology 5:4, 283-288
CrossRef125
Jeanette Lundin, Anders Österborg. (2004) Advances in the use of monoclonal antibodies in the therapy of chronic lymphocytic leukemia. Seminars in Hematology 41:3, 234-245
CrossRef126
Robert J Kreitman. (2004) Recombinant immunotoxins for the treatment of haematological malignancies. Expert Opinion on Biological Therapy 4:7, 1115-1128
CrossRef127
Francesco Lauria, Francesco Forconi. (2004) Towards the pharmacotherapy of hairy cell leukaemia. Expert Opinion on Pharmacotherapy 5:7, 1523-1533
CrossRef128
Yoshihisa Kaneda, Yasuo Tsutsumi, Yasuo Yoshioka, Haruhiko Kamada, Yoko Yamamoto, Hiroshi Kodaira, Shin-ichi Tsunoda, Takayuki Okamoto, Yohei Mukai, Hiroko Shibata, Shinsaku Nakagawa, Tadanori Mayumi. (2004) The use of PVP as a polymeric carrier to improve the plasma half-life of drugs. Biomaterials 25:16, 3259-3266
CrossRef129
Yasuo Oshima, Arinobu Tojo, Akio Fujimura, Yoshiyuki Niho, Shigetaka Asano. (2004) Potent receptor-mediated cytotoxicity of granulocyte colony-stimulating factor-Pseudomonas exotoxin, a fusion protein against myeloid leukemia cells. Biochemical and Biophysical Research Communications 319:2, 582-589
CrossRef130
Blanche H Mavromatis, Bruce D Cheson. (2004) Novel therapies for chronic lymphocytic leukemia. Blood Reviews 18:2, 137-148
CrossRef131
Arjan A. van de Loosdrecht, Peter C. Huijgens, Gert J. Ossenkoppele. (2004) Emerging antibody-targeted therapy in leukemia and lymphoma: current concepts and clinical implications. Anti-Cancer Drugs 15:3, 189-201
CrossRef132
Matthias Peipp, Domenica Saul, Karin Barbin, Joerg Bruenke, Susan J. Zunino, Michael Niederweis, Georg H. Fey. (2004) Efficient eukaryotic expression of fluorescent scFv fusion proteins directed against CD antigens for FACS applications. Journal of Immunological Methods 285:2, 265-280
CrossRef133
Hiroko Shibata, Shinsaku Nakagawa, Tadanori Mayumi, Yasuo Tsutsumi. (2004) Development of Novel Drug Delivery System (DDS) Technologies for Proteomic-Based Drug Development. Biological & Pharmaceutical Bulletin 27:10, 1483-1488
CrossRef134
TADEUSZ ROBAK. (2004) Monoclonal Antibodies in the Treatment of Chronic Lymphoid Leukemias. Leukemia & Lymphoma 45:2, 205-219
CrossRef135
David J. FitzGerald, Robert Kreitman, Wyndham Wilson, David Squires, Ira Pastan. (2004) Recombinant immunotoxins for treating cancer. International Journal of Medical Microbiology 293:7-8, 577-582
CrossRef136
Marc Azemar, Sirus Djahansouzi, Elke Jäger, Christine Solbach, Mathias Schmidt, Alexander B. Maurer, Klaus Mross, Clemens Unger, Gunter von Minckwitz, Peter Dall, Bernd Groner, Winfried S. Wels. (2003) Regression of Cutaneous Tumor Lesions in Patients Intratumorally Injected with a Recombinant Single-chain Antibody-toxin Targeted to ErbB2/HER2. Breast Cancer Research and Treatment 82:3, 155-164
CrossRef137
Michael M. Quigley, Kelly J. Bethel, Robert W. Sharpe, Alan Saven. (2003) CD52 expression in hairy cell leukemia. American Journal of Hematology 74:4, 227-230
CrossRef138
Paul Virgo, Patricia A. Denning-Kendall, Connie L. Erickson-Miller, Sakon Singha, Roger Evely, Jill M. Hows, Sylvie D. Freeman. (2003) Identification of the CD33-related Siglec receptor, Siglec-5 (CD170), as a useful marker in both normal myelopoiesis and acute myeloid leukaemias. British Journal of Haematology 123:3, 420-430
CrossRef139
Satoshi Nagata, Giuliana Salvatore, Ira Pastan. (2003) DNA immunization followed by a single boost with cells: a protein-free immunization protocol for production of monoclonal antibodies against the native form of membrane proteins. Journal of Immunological Methods 280:1-2, 59-72
CrossRef140
Joanne L Casey, Andrew M Coley. (2003) Cambridge Healthtech Institute’s 4th Annual Recombinant Antibodies Conference. Expert Opinion on Biological Therapy 3:5, 859-862
CrossRef141
Grant R. Goodman, Kelly J. Bethel, Alan Saven. (2003) Hairy cell leukemia: an update. Current Opinion in Hematology 10:4, 258-266
CrossRef142
Ke Liu. (2003) The case for cancer immunotherapy. Drug Discovery Today 8:12, 530-531
CrossRef143
Alessandra Cesano, Urte Gayko. (2003) CD22 as a target of passive immunotherapy. Seminars in Oncology 30:2, 253-257
CrossRef144
Robert J Kreitman, Ira Pastan. (2003) Immunobiological treatments of hairy-cell leukaemia. Best Practice & Research Clinical Haematology 16:1, 117-133
CrossRef145
Gillian Payne. (2003) Progress in immunoconjugate cancer therapeutics. Cancer Cell 3:3, 207-212
CrossRef146
Grant R Goodman, Ernest Beutler, Alan Saven. (2003) Cladribine in the treatment of hairy-cell leukaemia. Best Practice & Research Clinical Haematology 16:1, 101-116
CrossRef147
Shahid Ahmed, Kanti R Rai. (2003) Interferon in the treatment of hairy-cell leukemia. Best Practice & Research Clinical Haematology 16:1, 69-81
CrossRef148
Bertrand Coiffier. (2003) Monoclonal antibodies combined to chemotherapy for the treatment of patients with lymphoma. Blood Reviews 17:1, 25-31
CrossRef149
Samuel Murray, Helena Linardou. (2003) Therapeutic anticancer antibodies. Expert Opinion on Therapeutic Patents 13:2, 177-222
CrossRef150
Ulrich Mey, John Strehl, Marcus Gorschlüter, Carsten Ziske, Axel Glasmacher, Hans Pralle, Ingo Schmidt-Wolf. (2003) Advances in the treatment of hairy-cell leukaemia. The Lancet Oncology 4:2, 86-94
CrossRef151
P. Nygren, R. Larsson. (2003) Overview of the clinical efficacy of investigational anticancer drugs. Journal of Internal Medicine 253:1, 46-75
CrossRef152
Catherine Thieblemont, Bertrand Coiffier. (2002) Combination of Chemotherapy and Monoclonal Antibodies for the Treatment of Lymphoma. International Journal of Hematology 76:5, 394-400
CrossRef153
Kensei Tobinai. (2002) Monoclonal Antibody Therapy for B-Cell Lymphoma: Clinical Trials of an Anti-CD20 Monoclonal Antibody for B-Cell Lymphoma in Japan. International Journal of Hematology 76:5, 411-419
CrossRef154
D.J Allsup, J.C Cawley. (2002) The diagnosis and treatment of hairy-cell leukaemia. Blood Reviews 16:4, 255-262
CrossRef155
Arthur E Frankel. (2002) Receptor upregulation enhances cell surface receptor targeted therapies. Leukemia Research 26:12, 1069-1071
CrossRef156
Robert J Kreitman. (2002) Recombinant fusion toxins for cancer treatment. Expert Opinion on Biological Therapy 2:8, 785-791
CrossRef157
L. Lacotte-Thierry, F. Guilhot. (2002) Interféron et hématologie. La Revue de Médecine Interne 23, 481S-488S
CrossRef158
Kensei Tobinai. (2002) Rituximab and other emerging monoclonal antibody therapies for lymphoma. Expert Opinion on Emerging Drugs 7:2, 289-302
CrossRef159
Theresa M. Allen. (2002) Ligand-targeted therapeutics in anticancer therapy. Nature Reviews Cancer 2:10, 750-763
CrossRef160
Martin S Tallman. (2002) Advancing the treatment of hematologic malignancies through the development of targeted interventions. Seminars in Hematology 39:4, 1-5
CrossRef161
Shimei Gong, Xin Lu, Yongsheng Xu, Carol F. Swiderski, Craig T. Jordan, Jeffrey A. Moscow. (2002) Identification of OCT6 as a novel organic cation transporter preferentially expressed in hematopoietic cells and leukemias. Experimental Hematology 30:10, 1162-1169
CrossRef162
Martin S Tallman. (2002) Monoclonal antibody therapies in leukemias. Seminars in Hematology 39:4, 12-19
CrossRef163
James M. Foran. (2002) Antibody-based therapy of non-Hodgkin's lymphoma. Best Practice & Research Clinical Haematology 15:3, 449-465
CrossRef164
Joseph C. Shanahan, E.William St. Clair. (2002) Tumor Necrosis Factor-α Blockade: A Novel Therapy for Rheumatic Disease. Clinical Immunology 103:3, 231-242
CrossRef165
Giuliana Salvatore, Satoshi Nagata, Marc Billaud, Massimo Santoro, Giancarlo Vecchio, Ira Pastan. (2002) Generation and characterization of novel monoclonal antibodies to the Ret receptor tyrosine kinase. Biochemical and Biophysical Research Communications 294:4, 813-817
CrossRef166
Marla Weetall, Mary Ellen Digan, Ronald Hugo, Sheba Mathew, Christine Hopf, Nicole Tart-Risher, Jin Zhang, Victor Shi, Fumin Fu, Denise Hammond-McKibben, Susan West, Richard Brack, Volker Brinkmann, Reinhard Bergman, David Neville, Philip Lake. (2002) T-cell depletion and graft survival induced by anti-human CD3 immunotoxins in human CD3?? transgenic mice. Transplantation 73:10, 1658-1666
CrossRef167
Robert J. Kreitman. (2002) Hairy Cell Leukemia. American Journal of Cancer 1:3, 189-203
CrossRef168
(2001) Treatment of Hairy-Cell Leukemia. New England Journal of Medicine 345:20, 1500-1501
Full Text169
&NA;. (2001) BL 22 and cladribine in hairy cell leukaemia. Inpharma Weekly &NA;:1315, 4
CrossRef170
Susanna M Rybak, Dianne L Newton. (2001) Antibody targeted therapeutics for lymphoma: new focus on the CD22 antigen and RNA. Expert Opinion on Biological Therapy 1:6, 995-1003
CrossRef171
&NA;. (2001) BL 22 demonstrates promising activity in hairy cell leukaemia. Inpharma Weekly &NA;:1299, 8
CrossRef172
Schnipper, Lowell E., Strom, Terry B., . (2001) A Magic Bullet for Cancer — How Near and How Far?. New England Journal of Medicine 345:4, 283-284
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