Adoptive cell transfer: examining the potential of a T cell-mediated therapy for metastatic melanoma

Abstract

Adoptive cell transfer techniques identify and isolate patient anti-tumor lymphocytes in vitro followed by ex vivo expansion of these tumor specific T cells. Identification and isolation of lymphocytes from patient tumors allows for the selection of anti-tumor lymphocytes that are highly specific for individual tumor antigens. Furthermore, recombinant technology allows for engineering of chimeric antigen receptors (CARs) which allow these T cells to target multiple tumor antigens. Techniques involving ex vivo growth lead to a 1,000- to 5,000-fold increase in numbers of lymphocytes. Cultured lymphocytes can then be infused via IV and growth maintained with administration of exogenous IL-2. Cancer patients are then monitored for both immunological activity as well as any adverse cytokine reactions. We looked at several trial studies for the application of adoptive cell transfer in metastatic melanoma compare the efficacy of the regimen to other established melanoma treatments. Adoptive transfer has proven to be effective for patients with late stage melanoma, however, the aim of this study was to examine some of the challenges in creating an effective standard protocol for adaptation in clinical settings, including difficulty in obtaining significant cell populations from tumors, challenges in the proliferation of these tumor-infiltrating lymphocytes (TIL) and determination of antigen-specificity, i.e. facilitation of a simplified and quicker approach to the therapy.