Practical considerations for chimeric antigen receptor design and delivery.

INTRODUCTION: The development of chimeric antigen receptor (CAR)-modified immune cells has become a highly active field of research since the introduction of this approach in 1989. New ideas are constantly being proposed and tested, resulting in CARs that are more effective and specialized. Areas covered: Many aspects of CAR design and administration can be varied in order to achieve the best possible outcomes; optimization of this therapeutic schema is an active area of research. Here, the authors summarize the work that has been carried out thus far to assess different adaptations for each portion of the CAR itself. They also discuss the various methods used for CAR transgene transfer into effector cells. Expert opinion: While the field has made significant advancements in terms of expansion and testing of the variations available for CAR therapy, it remains difficult to ascertain which options are truly superior and under what conditions. Continued research in this area, as well as in aspects such as improving the safety profile and the anti-tumor potency of CARs, will be required to bring this therapy from early-phase clinical trials to standard of care as an effective treatment for a broad range of tumor types.