Engineering T cells for adoptive therapy: outsmarting the tumor

Abstract

Adoptive transfer of T cells gene-engineered with antigen-specific receptors, whether it be chimeric antigen receptors (CARs) or T cell receptors (TCRs), has proven its feasibility and therapeutic potential in the treatment of tumors. Despite clinical successes, the majority of patients experiences no or non-sustainable clearance of solid tumors, which is attributed to local T cell evasive mechanisms. A rapidly expanding understanding of molecular and cellular events that contribute to a reduction in numbers and/or activation of intra-tumor T cells has facilitated the development of gene-engineering strategies, enabling T cells to counter immune tolerance. Here, we present an overview of gene-engineering approaches and considerations to improve tumor-selectivity and effectiveness of adoptively transferred T cells.