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ASH 2014: Chimeric antigen receptor T cells shows promise in lymphoma
by Thomas R. Collins: The use of chimeric antigen receptor T-cells — in which a patient’s own T cells are modified to fight cancer cells — is showing good results in lymphoma patients, according to early results in small studies. The exciting new approach to combating hematologic malignancies was discussed in a special scientific symposium here at the 56th Annual Meeting of the American Society of Hematology.
In adoptive cell transfer, T-cells are collected from a patient and then genetically engineered to produce special receptors, known as chimeric antigen receptors (CAR). These CAR proteins allow the T-cells to recognize a specific antigen on a tumor cell. The CAR T-cells are reproduced in a lab and then infused back into the patient, continuing to multiply and, hopefully, killing cancer cells. The modified T-cells have been called a “living drug” and have been seen to persist in the body for more than a decade.
Carl June, MD, Professor of Immunology, Pathology and Laboratory Medicine at the Abramson Cancer Center at the University of Pennsylvania, and a lead investigator in the field, said that serious adverse events have been unseen in more than 1,000 patient years in subjects given the treatment. “It’s a platform that is safe — in fact, safer than the chemotherapy that we routinely use for hematologic malignancies,” he said.
The first CAR T-cells have been modified to have CD19 receptors, and CD19 antigens are expressed “ubiquitously” on B-cell lymphomas, Dr. June said. A study out of the University of Pennsylvania has found that 10 out of 16 patients given CAR treatment have had either a complete or partial response, with 8 achieving a complete response. All five of the follicular lymphoma patients in the group responded to the therapy. (1) “There are durable responses,” Dr. June said. “No one has progressed after achieving a complete response…. The results are early but appear promising.”
T-cells adapted with different receptor types are in the early stages of being investigated, which could widen the applicability of the therapy. “This is the beginning of what will be a very large array of CARs,” he said. “In fact, we call it the CAR fleet.”
Steven Rosenberg, MD, PhD, Chief of Surgery at the National Cancer Institute, said that while the earliest work on CAR T-cells has been on hematologic malignancies, the therapy is showing promise in solid tumors as well. He envisions the possibility of crafting T-cells specific to each individual’s disease. “This field has been moving along at warp speed,” he said. “The identification and selected targeting of mutated antigens unique to each patient’s cancer may be a means to apply cell transfer immunotherapy to common epithelial cancers. In a sense, it’s the ultimate personalized therapy. Using a patient’s own cells to selectively target their own mutations.”
(1) Schuster, Svoboda, Nasta, et al. Phase IIa Trial of Chimeric Antigen Receptor Modified T Cells Directed Against CD19 (CTL019) in Patients with Relapsed or Refractory CD19+ Lymphomas. ASH 2014. Abstract 3087.
