The adoptive transfer of cultured T cells for patients with metastatic melanoma

T cells have been shown to be capable of rejecting a patient's tumor. Weak responses to current vaccines and the toxicity of exogenously administered cytokines limit the intensity of the T-cell response that can be actively generated in vivo. Adoptive T-cell transfer enhances an intrinsically weak immune response to cancer by activating and expanding tumor reactive T cells in vitro and manipulating the environment of the host at the time of transfer. One can frequently find tumor-reactive T cells in metastatic lesions in patients with melanoma, and expand them in vitro for readministration. When successful, this adoptive cellular immunotherapy has resulted in sustainable curative outcomes. Subsequently, the applicability of adoptive T-cell transfer has been greatly expanded by the development of methods to genetically engineer open-repertoire human T-cells to confer tumor reactivity. This re-direction of T-cell specificity can be achieved by introducing a variety of receptors that ligate tumor-associated antigens and then trigger the normal activation mechanism of T cells. Future T-cell engineering will add a new dimension by reprogramming T-cell functions for optimal tumor rejection. The antigens recognized by T cells, the techniques to procure and grow tumor reactive T cells, the conditioning of the recipient to optimize efficacy, and the results of clinical protocols are reviewed herein.