Chimeric Antigen Receptor-T-Cell Therapy in Hematology: Current Opportunities and Future Challenges

Chimeric antigen receptor-T cell (CAR-T) therapy is based on the ex vivo reprogramming of a patient’s own T cells with a CAR construct targeting cancer antigens. Subsequently, modified CAR-T cells are infused back into the patients, aiming to initiate an appropriate immune response and potentially eradicate tumor cells. CAR-T therapy has profoundly altered the treatment landscape of non-Hodgkin lymphoma, B-cell acute lymphoblastic leukemia, and multiple myeloma. Currently available CD19 and B-cell maturation antigen-directed CAR-T therapies have shown high overall response rate and durable remissions in patients who have failed standard therapies. Optimizing efficacy and reducing the risk of toxicities, however, have posed major challenges, limiting the success of this therapy. In this review, therefore, we discuss the obstacles facing CAR-T cell therapy, how these relate to our current understanding of CAR-T cell biology and approaches to enhance the clinical efficacy of smart T cell precision therapeutics.