Abstract

Adoptive immunotherapy with tumor infiltrating lymphocytes (TILs) is a potent therapy for metastatic melanoma. In this process, naturally occurring tumor reactive TILs that bear T-cell receptors (TCR) targeted against tumor cells are generated ex vivo and administrated into the patients. The generation of tumor-reactive T cells is not always possible in all of the patients. To overcome this limitation, we can now insert highly avid TCRs into T cells that can recognize tumor antigens. Genetic engineering of TCR genes into normal T cells is a powerful new strategy to generate large numbers of defined antigen-specific cells for therapeutic application. This approach has evolved beyond experimental stage into a clinical reality. The feasibility of TCR-engineered T cells has been shown to be an effective clinical strategy resulting in the regression of established tumors in recent clinical trials. In this review, we discuss the progress and prospects of TCR-engineered T cells as a therapeutic strategy for treating patients with melanoma and other cancers.

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