Correspondence
Cancer Immunotherapy
N Engl J Med 2008; 359:1072-1073September 4, 2008
- Article
To the Editor:
In his review of cancer immunology, Finn (June 19 issue)1 states that the results of immunotherapy involving intravenous administration of tumor-specific autologous T cells (adoptive cell therapy) are “marginal,” whereas the results of trials of cancer vaccines are “encouraging.” We do not believe this conclusion accurately reflects the state of the field.
In 1994, we reported a 34% objective response rate among patients with metastatic melanoma who were treated with adoptive cell therapy.2 These results have steadily improved. Adding lymphocyte-depleting chemotherapy before adoptive cell therapy increased the objective-response rate to 49%,3 and adding radiotherapy increased the objective-response rate to 72% (unpublished data). With the use of cancer vaccines, the objective-response rate ranges from 3 to 7%,4 and with the use of interleukin-2 or anti–cytotoxic T-lymphocyte–associated antigen 4, it ranges from 13 to 17%. Thus, adoptive cell therapy is the most effective immunotherapy in patients with metastatic melanoma.
We have seen no correlation between the bulk of disease and the likelihood of achieving an objective response. The recent report of regression of cancer when adoptive cell therapy was used with peripheral lymphocytes genetically engineered to express antitumor T-cell receptors holds promise for extending the use of adoptive cell therapy to patients with common epithelial cancers.5
5 ReferencesSteven A. Rosenberg, M.D., Ph.D.
Mark E. Dudley, Ph.D.
Nicholas P. Restifo, M.D.
National Cancer Institute, Bethesda, MD 20892
sar@nih.gov 1
Finn OJ . Cancer immunology. N Engl J Med 2008;358:2704-2715
Full Text | Web of Science | Medline2
Rosenberg SA ,Yannelli JR ,Yang JC , et al. Treatment of patients with metastatic melanoma using autologous tumor-infiltrating lymphocytes and interleukin 2. J Natl Cancer Inst 1994;86:1159-1166
CrossRef | Web of Science | Medline3
Dudley ME ,Wunderlich JR ,Robbins PF , et al. Cancer regression and autoimmunity in patients after clonal repopulation with anti-tumor lymphocytes. Science 2002;298:850-854
CrossRef | Web of Science | Medline4
Rosenberg SA ,Yang JC ,Restifo NP . Cancer immunotherapy: moving beyond current vaccines. Nat Med 2004;10:909-915
CrossRef | Web of Science | Medline5
Morgan RA ,Dudley ME ,Wunderlich JR , et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science 2006;314:126-129
CrossRef | Web of Science | Medline
To the Editor:
Hunder and colleagues (June 19 issue)1 report the successful adoptive transfer of CD4+ T cells against the melanoma-associated antigen NY-ESO-1 in a patient with metastatic melanoma, and in an accompanying Perspective article, Weiner2 speculates about the need to target immunosuppressive mechanisms to fulfill the potential of T-cell therapy in patients with cancer.
We wish to highlight an alternative strategy that combines adoptive T-cell therapy with oncolytic viral delivery. In mouse models, we have shown that antigen-nonspecific T cells loaded with oncolytic vesicular stomatitis virus efficiently delivered the virus to metastatic lymph nodes, even in preimmune mice; this leads to tumor clearance associated with antitumor immune priming.3 The loading of antigen-specific T cells with vesicular stomatitis virus enhanced the delivery of the virus to lung tumors,4 and the associated proinflammatory tumor microenvironment enhanced antigen-specific T-cell proliferation and survival within the tumor. The failure of adoptively transferred T-cell clones to persist has previously been a limiting factor.5 Combining adoptive T-cell therapy and oncolytic viral delivery may synergistically potentiate both forms of treatment.
5 ReferencesRobin Prestwich, M.D.
Cancer Research Clinical Centre, Leeds LS9 7TF, United KingdomRichard Vile, Ph.D.
Mayo Clinic, Rochester, MN 55905Alan Melcher, M.D., Ph.D.
Cancer Research Clinical Centre, Leeds LS9 7TF, United Kingdom
alan.melcher@cancer. org. uk 1
Hunder NN ,Wallen H ,Cao J , et al. Treatment of metastatic melanoma with autologous CD4+ T cells against NY-ESO-1. N Engl J Med 2008;358:2698-2703
Full Text | Web of Science | Medline2
Weiner LM . Cancer immunotherapy -- the endgame begins. N Engl J Med 2008;358:2664-2665
Full Text | Web of Science | Medline3
Qiao J ,Kottke T ,Willmon C , et al. Purging metastases in lymphoid organs using a combination of antigen-nonspecific adoptive T cell therapy, oncolytic virotherapy and immunotherapy. Nat Med 2008;14:37-44
CrossRef | Web of Science | Medline4
Qiao J ,Wang H ,Kottke T , et al. Loading of oncolytic vesicular stomatitis virus onto antigen-specific T cells enhances the efficacy of adoptive T-cell therapy of tumors. Gene Ther 2008;15:604-616
CrossRef | Web of Science | Medline5
Mackensen A ,Meidenbauer N ,Vogl S ,Laumer M ,Berger J ,Andreesen R . Phase I study of adoptive T-cell therapy using antigen-specific CD8+ T cells for the treatment of patients with metastatic melanoma. J Clin Oncol 2006;24:5060-5069
CrossRef | Web of Science | Medline
Author/Editor Response
Prestwich and colleagues comment on one of the many interesting and promising strategies that have been proposed to enhance immune-mediated tumor destruction. Their approach alters the balance between immune activation and tumor-mediated immune evasion or immune suppression to achieve antitumor effects, possibly by providing powerful signals for immune activation in a microenvironment containing tumor. Their approach may elicit clinical responses in patients with cancer. However, it is at least as likely that understanding and neutralizing tumor-directed immune suppression will be important for the development of routinely effective cancer immunotherapy.
Louis M. Weiner, M.D.
Georgetown University Medical Center, Washington, DC 20016- Citing Articles (6)
Citing Articles
1
Fabrice Le Boeuf, Nima Niknejad, Jiahu Wang, Rebecca Auer, Johanne I. Weberpals, John C. Bell, Jim Dimitroulakos. (2012) Sensitivity of cervical carcinoma cells to vesicular stomatitis virus-induced oncolysis: Potential role of human papilloma virus infection. International Journal of Cancern/a-n/a
CrossRef2
M.G. Bourke, S. Salwa, K.J. Harrington, M.J. Kucharczyk, P.F. Forde, M. de Kruijf, D. Soden, M. Tangney, J.K. Collins, G.C. O’Sullivan. (2011) The emerging role of viruses in the treatment of solid tumours. Cancer Treatment Reviews 37:8, 618-632
CrossRef3
Els M. E. Verdegaal, Marten Visser, Tamara H. Ramwadhdoebé, Caroline E. Minne, Jeanne A. Q. M. J. Steijn, Ellen Kapiteijn, John B. A. G. Haanen, Sjoerd H. Burg, Johan W. R. Nortier, Susanne Osanto. (2011) Successful treatment of metastatic melanoma by adoptive transfer of blood-derived polyclonal tumor-specific CD4+ and CD8+ T cells in combination with low-dose interferon-alpha. Cancer Immunology, Immunotherapy 60:7, 953-963
CrossRef4
David L. A. Figueiredo, Rui C. M. Mamede, Giulio C. Spagnoli, Wilson A. Silva, Marco Zago, Luciano Neder, Achim A. Jungbluth, Fabiano P. Saggioro. (2011) High expression of cancer testis antigens MAGE-A, MAGE-C1/CT7, MAGE-C2/CT10, NY-ESO-1, and gage in advanced squamous cell carcinoma of the larynx. Head & Neck 33:5, 702-707
CrossRef5
Eun Sook Hwang. (2010) This month in APR. Archives of Pharmacal Research 33:11, 1699-1701
CrossRef6
Michele L. Martin, Erika M. Wall, Emily Sandwith, Adam Girardin, Katy Milne, Peter H. Watson, Brad H. Nelson. (2010) Density of tumour stroma is correlated to outcome after adoptive transfer of CD4+ and CD8+ T cells in a murine mammary carcinoma model. Breast Cancer Research and Treatment 121:3, 753-763
CrossRef
