Tumor-Infiltrating Lymphocytes in Melanoma
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Adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) is arguably the most effective treatment for patients with metastatic melanoma. With higher response rates than ipilimumab or IL-2, and longer durations of response than vemurafenib, TIL therapy carries the potential to transform current outcomes in melanoma, while also defining the way cell-based immunotherapy gets incorporated into mainstream cancer treatment. This paper will review the current state of TIL therapy in melanoma, the strategies to improve its efficacy, the current obstacles, and future directions to expand the availability of TIL to the general patient population.
KeywordsTumor-infiltrating lymphocytes TIL Adoptive cell therapy T cell Melanoma Immunotherapy
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 4.•• Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011;17:4550–7. This paper presents the most comprehensive long-term data on clinical responses in patients treated with TIL. PubMedCrossRefGoogle Scholar
- 19.• Boni A, Cogdill AP, Dang P, Udayakumar D, Njauw CN, Sloss CM, et al. Selective BRAFV600E inhibition enhances T-cell recognition of melanoma without affecting lymphocyte function. Cancer Res. 2010;70:5213–9. An important paper that demonstrates BRAF inhibition increases tumor antigen expression, providing the scientific basis for a potential synergy between targeted therapy and immunotherapy. PubMedCrossRefGoogle Scholar
- 21.Koya RC, Mok S, Otte N, Blacketor KJ, Comin-Anduix B, Tumeh PC, et al. BRAF inhibitor vemurafenib improves the antitumor activity of adoptive cell immunotherapy. Cancer Res. 2012.Google Scholar
- 29.Donia M, Junker N, Ellebaek E, Andersen MH, Straten PT, Svane IM. Characterization and comparison of "Standard" and "Young" tumor infiltrating lymphocytes for adoptive cell therapy at a Danish Translational Research Institution. Scand J Immunol. 2011.Google Scholar
- 30.Sarnaik A. Costimulatory effect of agonistic 4-1BB antibody on proliferation and effector phenotype of tumor-infiltrating lymphocytes in melanoma. 2012 ASCO Annual Meeting; 2012; Chicago. 2012.Google Scholar
- 39.Yee C, Thompson JA, Byrd D, Riddell SR, Roche P, Celis E, et al. Adoptive T cell therapy using antigen-specific CD8+ T cell clones for the treatment of patients with metastatic melanoma: in vivo persistence, migration, and antitumor effect of transferred T cells. Proc Natl Acad Sci U S A. 2002;99:16168–73.PubMedCrossRefGoogle Scholar
- 42.Cancer Epidemiology in Older Adolescents & Young Adults. SEER AYA Monograph; 2007. p. 53–7.Google Scholar
- 43.National Cancer Institute. [cited]; Available at http://seer.cancer.gov/csr/1975_2008/ ; based on November 2010 SEER data submission, posted to the SEER web site, 2011.