Cancer Insights: The potential of CAR-T cells to fight prostate cancer
March 2, 2015 | by Sumanta Kumar Pal M.D.
Pick up any biotech industry report and you’re guaranteed to come across one term repeatedly – CAR-T therapy. A fierce competition is now underway to bring CAR-T treatments to market – several companies (Juno, Novartis, Kite and Cellectis, to name a few) have major stakes in the race. I’ve found the CAR-T buzz has also penetrated the clinic -- not a day goes by that I don’t have a conversation with a patient regarding this emerging technology.
So what is CAR-T? Essentially, it’s an engineered immune cell (called a T cell) that has on its surface a highly specific protein called a chimeric antigen receptor (CAR). These “souped up” immune cells can mount a potent and highly specific attack against tumors.
Last year, a group of researchers from the University of Pennsylvania published results in the New England Journal of Medicine pertaining to 30 patients who had received CAR-T therapies. These patients were suffering from a relapse of acute lymphoblastic leukemia (ALL) and had failed standard treatments. The results were nothing short of remarkable – at six months following treatment, roughly two-thirds of patients remained free of disease.
These findings were a phenomenal leap forward for patients with this relatively rare disorder. A couple of roadblocks stand in the way of further development of CAR-T cells, however.
The first is the manufacturing processes involved – “scaling up” the production of this highly specific therapy will require extensive resources. It’s not possible to simply stock the shelves with drugs of this kind – CAR-T therapy is essentially a personalized drug made for individual patients.
The second issue facing CAR-T therapy is how to make it more applicable to cancer patients at large. In 2015, just over 6,000 cases of ALL will be diagnosed, representing less than 1 percent of all cancer diagnoses. Although CAR-T has certainly made a footprint in ALL, will it make a splash in other more common cancer types?
One researcher leading this drive to maximize the potential of CAR-T therapy is Stephen J. Forman, M.D., the Francis & Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation at City of Hope. Forman is a pioneer of bone marrow and stem cell transplants, which several decades ago seemed a far-fetched prospect. Like CAR-T therapy, bone marrow transplant was a highly personalized therapy applied in a limited scope of diseases. Over the course of time, the indications have gradually expanded, allowing this life-saving therapy to be applied in hundreds of thousands of patients.
Now Forman is leading a project that aims to utilize CAR-T therapy in patients with advanced prostate cancer. Forman’s approach differs in that he will combine CAR-T cells with other agents that will augment the body’s immune system.
“One of the things we’ve built into our prostate cancer immune therapy is to address not just the cells that could kill the cancer, but the cancer’s ability to suppress the immune system,” Forman said. This “combined modality” therapy, as he terms it, may enhance the effect of CAR-T therapy. The project is fueled by a $1 million grant from the Prostate Cancer Foundation, which has backed many efforts to develop new prostate cancer drugs.
The realization of CAR-T therapy in prostate cancer could have an impact on the more than 220,000 men diagnosed with the disease annually in the U.S. Although the issues of scalability remain, Forman said, City of Hope also faced this dilemma decades ago.
“When we first introduced bone marrow transplant, it was thought of as rogue and cavalier,” he said. “Now the procedure is being conducted in varying forms at cancer centers across the U.S.”
With his direction, CAR-T may enjoy the same fate.
Sumanta Kumar Pal, M.D., is an assistant professor in the Department of Medical Oncology & Therapeutics Research and co-director of the Kidney Cancer Program at City of Hope.
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