Immunotherapy pioneers Michel Sadelain, MD, PhD, of Memorial Sloan Kettering Cancer Center (MSK), and Carl June, MD, of the University of Pennsylvania, have published a seminal review of the current landscape of chimeric antigen receptor (CAR) therapy in the New England Journal of Medicine (NEJM). In the comprehensive review article, Drs. Sadelain and June highlight the emerging immunotherapy treatment for hematologic cancers known as CAR T cells, which was developed at MSK. The paper is the first in a series being published by NEJM. Known as Frontiers in Medicine, it will showcase ways that new technologies are influencing contemporary medicine and science.
The wide-ranging article reflects on the history of immuno-oncology and adoptive cell transfer in addition to the identification of CD19 as the first target and the creation of CD19 CAR T cells. While addressing the current landscape of CAR T therapies, the authors recognize the challenges and toxicities associated with treatment as well as the obstacles to broad implementation, although the authors stress that these challenges are not indictments of the therapeutic approach. On the contrary, the review provides a cautiously optimistic view of the future of CAR T therapy, noting that the efficacy of this treatment against B cell cancers is a good omen for the treatment of other hematologic cancers. In addition, rapidly evolving genetic engineering technologies, combined with synthetic biology, can now offer a wide range of possibilities to design T cells with enhanced functions.
Immunotherapy was born at MSK more than a century ago. Since then, Dr. Sadelain and MSK colleagues have led the effort to develop new immune-based treatments for cancer. Recent US Food and Drug Administration (FDA) approvals of CD19 CAR T cells for relapsed and refractory acute lymphoblastic leukemia and for diffuse large B cell lymphoma were the first form of gene-transfer therapy to gain commercial approval by the FDA. These genetically engineered T cells constitute a powerful new class of therapeutic agents that offer hope for curative responses in people with cancer. The authors note that the principles used here could also be used to design cell therapies targeted to treat other diseases and can likely lead to accelerated translation of engineered cell therapies for a plethora of inflammatory and regenerative medicine applications.