Cancer CARtography: charting out a new approach to cancer immunotherapy

Evaluation of: Davila ML, Riviere I, Wang X et al. Efficacy and toxicity management of 19-28z CAR T cell therapy in B cell acute lymphoblastic leukemia. Sci. Transl. Med. 6(224), 224ra25 (2014). Recently, chimeric antigen receptor (CAR) T-cell immunotherapy has entered clinical trials in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. 19-28z CAR T cells express a fusion protein comprised of an anti-CD19 mAb fused with CD28 costimulatory and CD3-zeta-chain signaling domains. The current paper demonstrates that administration of 19-28z CAR T cells in patients with relapsed or refractory B-ALL in a Phase I clinical trial has led to 88% of patients undergoing complete remission. Despite the benefits, CAR T-cell therapy is associated with cytokine release syndrome toxicities. The authors demonstrated criteria to diagnose severe cytokine release syndrome (sCRS) and treated sCRS with either high-dose steroids or with tocilizumab, an IL-6 receptor-specific mAb. Although both alleviated sCRS, steroid treatment negated the beneficial effects of CAR T-cell therapy, whereas tocilizumab did not. Taken together, CAR T-cell immunotherapy can be used as a safe and effective approach against tumors with known tumor-associated antigens.