Enhancing CAR T cell efficacy: the next step toward a clinical revolution?

Introduction: The field of immunotherapy has witnessed considerable progress over the last two decades. Beginning with the ability to conceptualize CAR T cell therapy as immunotherapeutic approach, to effortlessly genetically modifying T cells, we have now reached the stage of mass production for clinical needs, all within less than quarter of a century. Areas covered: CAR T cell therapy has been tremendously successful in acute leukemia patients, specifically even in relapsed/refractory disease states. However, similar success is yet to be realized in other malignancies. This review article covers the challenges encountered with the current CD19-targeted CARs, as well as specific obstacles faced by adoptive therapy in solid tumors. It also discusses various strategies to counteract these problems. Expert opinion: CD19-directed trials in the past decade have exposed vulnerabilities in the current CAR T cell design, particularly concerning safety aspects, antigen escape, and T cell persistence. Building on these lessons and factoring in the unique challenges associated with immunotherapy in solid tumors will help generate CARs designed for future trials. Also, research related to the production of allogeneic CAR T cell products will boost the patient reach of this unique technology and possibly reduce financial burden.