Thursday, May 17, 2018
Scientists at Memorial Sloan Kettering are investigating ways to develop effective CAR T cell therapies for solid tumors. Preliminary results from a clinical trial in people with mesothelioma indicate that an experimental CAR therapy is safe.
Chimeric antigen receptor (CAR) T cell therapy has shown great promise for the treatment of certain blood cancers, like leukemia and lymphoma. By contrast, using this method to treat solid tumors has been more challenging.
This week, Memorial Sloan Kettering researchers presented early results from a phase I clinical trial of CAR therapy in mesothelioma. This hard-to-treat cancer usually affects the tissue surrounding the lungs, called the pleura.
According to Prasad Adusumilli, a physician-scientist at MSK who is leading the trial, the CAR therapy proved safe and showed signs of efficacy in a small number of patients. Dr. Adusumilli presented these results at the annual meeting of the American Society of Gene and Cell Therapy, held this year in Chicago.
This trial included 12 patients: ten with pleural mesothelioma, one with metastatic lung cancer, and one with metastatic breast cancer. They received CAR T cells built to target a molecule called mesothelin found on the surface of the cancer cells. The CAR T cells were infused directly into the space between the pleura.
A few weeks after the CAR T infusion, seven patients received another immunotherapy treatment called pembrolizumab (Keytruda®). This drug, a type of checkpoint inhibitor, blocks a molecule on immune cells called PD-1 and boosts immune responses. Dr. Adusumilli and colleagues had previously shown that this combination was effective in treating cancer in mice.
Patients tolerated the CAR T treatment well. There were no CAR T–related side effects. Severe cytokine release syndrome, which is characterized by dangerously high fevers and has complicated CAR therapy for other cancers, did not occur in any of the patients.
One patient with mesothelioma who was treated with both CAR T cells and pembrolizumab had a complete response, as shown on a PET scan. The patient remains healthy, requiring no additional therapies, 12 months after receiving the CAR T cells. There is evidence that the CAR T cells are still present and active in the body.
Michel Sadelain, one of the main pioneers of CAR T therapy, calls the results “intriguing.” He adds, “This is good news for CAR therapy in solid tumors.”
Expanding the CAR Fleet
MSK scientists developed the first effective CAR T cells for cancer. These prototype cells are built with an activity-boosting molecule called CD28 and target a molecule on B-cell leukemia and lymphoma called CD19. This cell-surface molecule is a good target for CARs because it is found on all B-cell cancers but not on other tissues that are critical for life.
Mesothelin is a potentially good target for CARs because it is present abundantly on solid tumor cancer cells but minimally on normal tissues. In addition to mesothelioma, mesothelin is found on pancreatic cancer, triple-negative breast cancer, lung cancer, and others. Drs. Adusumilli and Sadelain designed the mesothelin-specific CARs used in this study.
“We are encouraged by these results,” Dr. Adusumilli says. “We hope they spur interest in the potential of CAR T cell therapy for solid tumors.”
The trial is still open and enrolling patients.
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