Novartis and the University of Pennsylvania signed an exclusive global research and licensing partnership that aims to accelerate the commercialization of CAR T-cell cancer therapies.

With some dramatic recent successes in early clinical trials, chimeric antigen receptor (CAR) T-cell cancer treatments “have reached a tipping point in a new paradigm of therapy,” says Bruce Levine, PhD, associate professor and director of the Clinical Cell and Vaccine Production Facility at the University of Pennsylvania (UPenn) in Philadelphia.

“However, for many years while we've been working on this technology, we and others have wondered if biotech and pharmaceutical companies would ever get into this personalized therapy,” Levine notes.

The question was answered for Levine, his colleague Carl June, MD, and other UPenn researchers in an exclusive global research and licensing partnership with Novartis announced in August that aims to accelerate the commercialization of CAR T-cell therapies. Although complete financial details were not disclosed, Novartis will provide about $20 million in funding for a Center for Advanced Cellular Therapies at UPenn that will be directed by June.

In CAR T-cell cancer treatment, a form of adoptive cell transfer, a patient's T cells are removed and genetically modified to express a chimeric protein that couples a targeted antibody-binding domain on the cell surface with stimulatory domains inside the cell that activate its response.

The individualized cell processing required to generate CAR T cells “is a big source of the skepticism from companies or other stakeholders that are more interested in small molecules or vaccines that are off the shelf,” says Levine. “One has to look at this as a totally different paradigm, akin to stem cell transplants or heart transplants or surgery—it's one dose or one procedure per patient.”

The procedure may be strikingly effective. In a 2011 New England Journal of Medicine (NEJM)paper, the UPenn team reported on treating 3 patients with chronic lymphocytic leukemia (CLL), a B-cell cancer, with CD4+ T cells that were reengineered to bind to the CD19 protein found on normal B cells and plasma cells. In early results, 2 of the patients achieved complete remission. The number of cells expanded in vivo more than 1,000-fold, and some of the cells have persisted as memory T cells for at least 20 months, Levine says.

Investigators at Novartis and UPenn will work jointly to advance this treatment toward a successful commercial therapy for CLL, to employ it against other leukemias as well as lymphomas, to expand the approach to other tumor antigens, and to improve the understanding of biomarkers and assessment techniques.

“Our interest was piqued by the NEJM paper,” says William Sellers, MD, vice president of oncology research at Novartis Institutes for Biomedical Research in Cambridge, MA. “Not only did patients appear to have complete responses but the responses seemed very durable, and even next-generation sequencing had trouble detecting the most minimal residual cancer cell disease state.”

“We have not been a big player in cancer immunotherapy, and this gives us a huge opportunity to become a significant contributor in the field, paired with a world leader,” Sellers adds. “It's a unique collaboration, covering the gamut from target discovery to clinical application and even in some areas to manufacturing.”

“While we have been fortunate to be able to see striking clinical results in a small number of leukemia patients, this collaboration with Novartis will enable us to treat many more patients and to take this technology forward, we hope, to FDA [U.S. Food and Drug Administration] approval,” comments Levine.