Cancer immunotherapy with CAR T cells: well-trodden paths and journey along lesser-known routes

Abstract

Chimeric antigen receptor (CAR) T cell therapy is a clinically approved cancer immunotherapy approach using genetically engineered T cells. The success of CAR T cells has been met with challenges regarding efficacy and safety. Although a broad spectrum of CAR T cell variants and applications is emerging, this review focuses on CAR T cells for the treatment of cancer. In the first part, the general principles of adoptive cell transfer, the architecture of the CAR molecule, and the effects of design on function are presented. The second part describes five conceptual challenges that hinder the success of CAR T cells; immunosuppressive tumour microenvironment, T cell intrinsic properties, tumour targeting, manufacturing cellular product, and immune-related adverse events. Throughout the review, selected current approaches to address these issues are presented.

Keywords

• chimeric antigen receptor
• adoptive cell therapy
• cancer
• cellular immunotherapy
• gene-engineered immune cells