Correspondence

Patient-Specific Dendritic-Cell Vaccines for Metastatic Melanoma

N Engl J Med 2006; 355:1179-1181September 14, 2006

Article

To the Editor:

We are investigating the safety and efficacy of patient-specific vaccines derived from short-term autologous tumor-cell lines in the treatment of melanoma.1 In our current trial, patients with distant metastatic or recurrent regional melanoma are candidates for the receipt of an investigational vaccine consisting of autologous dendritic cells that have been incubated with irradiated autologous tumor cells from a proliferating cell culture and then suspended in granulocyte–macrophage colony-stimulating factor. The vaccine is administered subcutaneously once a week for 3 weeks, then monthly for 5 months.2 Of the first 21 patients enrolled, 18 are alive a median of 3 years (range, 2 to 5) after starting the vaccine therapy. The clinical courses of six of these patients are summarized in Table 1Table 1Summary of Diagnoses and Clinical Courses in Six Patients Who Received Patient-Specific Dendritic-Cell Vaccine for Metastatic Melanoma.. These six patients, all of whom had either extensive metastatic disease or repeated regional recurrences despite multiple therapies, are currently disease-free 24 to 58 months after the completion of the therapy.

This result was rarely observed in our previous trial of an autologous tumor-cell vaccine that did not include dendritic cells.3 Although all the patients in the current trial received a patient-specific autologous dendritic-cell vaccine, we cannot conclude that the vaccine alone produced the favorable outcomes, since all the patients had undergone more than one type of treatment. The long survival of the six patients is unusual, especially given the failure of multiple therapeutic interventions to prevent repeated recurrences in five of them and the extent of widespread metastatic disease in the sixth.

Robert O. Dillman, M.D.
Senthamil R. Selvan, Ph.D.
Patric M. Schiltz, Ph.D.
Hoag Cancer Center, Newport Beach, CA 92658
rdillman@hoaghospital.org

3 References

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   Dillman RO, Nayak SK, Beutel L. Establishing in vitro cultures of autologous tumor cells for use in active specific immunotherapy. J Immunother 1993;14:65-69
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   Dillman RO, DeLeon C, Beutel LD, et al. Short-term autologous tumor cell lines for the active specific immunotherapy of patients with metastatic melanoma. Crit Rev Oncol Hematol 2001;39:115-123
   CrossRef | Web of Science | Medline

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   Dillman RO, Selvan SR, Schiltz PM, et al. Phase I/II trial of melanoma patient-specific vaccine of proliferating autologous tumor cells, dendritic cells, and GM-CSF: planned interim analysis. Cancer Biother Radiopharm 2004;19:658-665
   Web of Science | Medline

Citing Articles (14)

Citing Articles

1. 1

   Robert O. Dillman, Gary B. Fogel, Andrew N. Cornforth, Senthamil R. Selvan, Patric M. Schiltz, Carol DePriest. (2011) Features Associated with Survival in Metastatic Melanoma Patients Treated with Patient-Specific Dendritic Cell Vaccines. Cancer Biotherapy & Radiopharmaceuticals 26:4, 407-415
   CrossRef

2. 2

   Oliver Klein, Christopher Schmidt, Ashley Knights, Ian D Davis, Weisan Chen, Jonathan Cebon. (2011) Melanoma vaccines: developments over the past 10 years. Expert Review of Vaccines 10:6, 853-873
   CrossRef

3. 3

   Andrew N. Cornforth, Abner W. Fowler, Denysha J. Carbonell, Eric Fan, Robert O. Dillman. (2011) Characterization of Interferon-γ–Treated Melanoma Tumor Cells for Use in Dendritic Cell-Based Immunotherapy. Cancer Biotherapy & Radiopharmaceuticals 26:3, 345-351
   CrossRef

4. 4

   Robert O. Dillman. (2011) Cancer Immunotherapy. Cancer Biotherapy & Radiopharmaceuticals 26:1, 1-64
   CrossRef

5. 5

   A. N. Cornforth, A. W. Fowler, D. J. Carbonell, R. O. Dillman. (2011) Resistance to the proapoptotic effects of interferon-gamma on melanoma cells used in patient-specific dendritic cell immunotherapy is associated with improved overall survival. Cancer Immunology, Immunotherapy 60:1, 123-131
   CrossRef

6. 6

   Robert O. Dillman, Andreea A. Nanci, Scott T. Williams, Richard B. Kim, Russell L. Hafer, Colleen L. Coleman, Peter C. Wang, Christopher M. Duma, Peter V. Chen, Senthamil R. Selvan, Andrew N. Cornforth, Carol DePriest. (2010) Durable Complete Response of Refractory, Progressing Metastatic Melanoma After Treatment with a Patient-Specific Vaccine. Cancer Biotherapy & Radiopharmaceuticals 25:5, 553-557
   CrossRef

7. 7

   Andrew N. Cornforth, Gregory J. Lee, Abner W. Fowler, Denysha J. Carbonell, Robert O. Dillman. (2009) Increases in Serum TARC/CCL17 Levels Are Associated with Progression-Free Survival in Advanced Melanoma Patients in Response to Dendritic Cell-Based Immunotherapy. Journal of Clinical Immunology 29:5, 657-664
   CrossRef

8. 8

   Robert O. Dillman, Senthamil R. Selvan, Patric M. Schiltz, Edward F. McClay, Neil M. Barth, Carol DePriest, Cristina de Leon, Cheryl Mayorga, Andrew N. Cornforth, Kanoe Allen. (2009) Phase II Trial of Dendritic Cells Loaded with Antigens from Self-Renewing, Proliferating Autologous Tumor Cells as Patient-Specific Antitumor Vaccines in Patients with Metastatic Melanoma: Final Report. Cancer Biotherapy & Radiopharmaceuticals 24:3, 311-319
   CrossRef

9. 9

   Mojca Skoberne, Alice Yewdall, Keith S. Bahjat, Emmanuelle Godefroy, Peter Lauer, Edward Lemmens, Weiqun Liu, Will Luckett, Meredith Leong, Thomas W. Dubensky, Dirk G. Brockstedt, Nina Bhardwaj. (2008) KBMA Listeria monocytogenes is an effective vector for DC-mediated induction of antitumor immunity. Journal of Clinical Investigation 118:12, 3990-4001
   CrossRef

10. 10

    M. Palma, L. Adamson, L. Hansson, P. Kokhaei, R. Rezvany, H. Mellstedt, A. Österborg, A. Choudhury. (2008) Development of a dendritic cell-based vaccine for chronic lymphocytic leukemia. Cancer Immunology, Immunotherapy 57:11, 1705-1710
    CrossRef

11. 11

    Patric M. Schiltz, Robert O. Dillman, Catharina M. Korse, James M. Cubellis, Gregory J. Lee, Gijsbert C. De Gast. (2008) Lack of Elevation of Serum S100B in Patients with Metastatic Melanoma as a Predictor of Outcome After Induction with an Autologous Vaccine of Proliferating Tumor Cells and Dendritic Cells. Cancer Biotherapy & Radiopharmaceuticals 23:2, 214-221
    CrossRef

12. 12

    Patric M. Schiltz, Gregory J. Lee, Jian Gang Zhang, Neil Hoa, H. Terry Wepsic, Robert O. Dillman, Martin R. Jadus. (2007) Human Allogeneic and Murine Xenogeneic Dendritic Cells Are Cytotoxic to Human Tumor Cells via Two Distinct Pathways. Cancer Biotherapy & Radiopharmaceuticals 22:5, 672-683
    CrossRef

13. 13

    Robert O. Dillman, Carol DePriest, Cristina DeLeon, Neil M. Barth, Lee S. Schwartzberg, Linda D. Beutel, Patric M. Schiltz, Shankar K. Nayak. (2007) Patient-Specific Vaccines Derived from Autologous Tumor Cell Lines as Active Specific Immunotherapy: Results of Exploratory Phase I/II Trials in Patients with Metastatic Melanoma. Cancer Biotherapy & Radiopharmaceuticals 22:3, 309-321
    CrossRef

14. 14

    Fabrício F. Costa, Katarina Le Blanc, Bertha Brodin. (2007) Concise Review: Cancer/Testis Antigens, Stem Cells, and Cancer. STEM CELLS 25:3, 707-711
    CrossRef