Chimeric antigen receptor (CAR)-engineered lymphocytes for cancer therapy

Introduction: Chimeric antigen receptors (CARs) usually combine the antigen binding site of a monoclonal antibody with the signal activating machinery of a T cell, freeing antigen recognition from MHC restriction and thus breaking one of the barriers to more widespread application of cellular therapy. Similar to treatment strategies employing monoclonal antibodies, T cells expressing CARs are highly targeted, but additionally offer the potential benefits of active trafficking to tumor sites, in vivo expansion and long-term persistence. Furthermore, gene transfer allows the introduction of countermeasures to tumor immune evasion and of safety mechanisms. Areas covered: The basic structure of so-called first and later generation CARs and their potential advantages over other immune therapy systems. How these molecules can be grafted into immune cells (including retroviral and non-retroviral transduction methods) and strategies to improve the in vivo persistence and function of immune cells expressing CARs. Examples of tumor-associated antigens that have been targeted in preclinical models and clinical experience with these modified cells. Safety issues surrounding CAR gene transfer into T cells and potential solutions to them. Expert opinion: Because of recent advances in immunology, genetics and cell processing, CAR-modified T cells will likely play an increasing role in the cellular therapy of cancer, chronic infections and autoimmune disorders.