Is antigen specificity the key to efficient adoptive T-cell therapy?

Abstract

Adoptive transfer of T cells remains a promising approach in melanoma. Initial clinical trials performed with polyclonal tumor-infiltrating lymphocyte gave limited clinical results. Nonetheless, encouraging results have been reported in adjuvant setting (stage III melanoma), and when tumor-infiltrating lymphocytes were associated with lymphodepleting regimens. Specificity of adoptive cell therapy has been achieved with the infusion of antigen specific cytotoxic T-lymphocyte clones, associated with some clinical responses. Antigen specificity can also be obtained by the allogeneic transfer of high-avidity T-cell receptors into autologous T cells. We propose an alternative strategy based on the selection of antigen-specific T cells with magnetic beads coated with HLA-peptide multimers. Future improvements of adoptive melanoma immunotherapy may be achieved by its association with other therapeutic strategies such as targeted therapy against signaling pathways.