Very few effective treatment options are available for patients with recurrent ovarian cancer and other solid tumors, but researchers are trying to change that.
Scientists at City of Hope recently published preclinical research in the journal Nature Communications demonstrating that a chimeric antigen receptor (CAR)-engineered T cell therapy worked against ovarian cancer in the laboratory and in preclinical models.
“City of Hope’s research helped develop CAR T cell therapies for blood cancers, and these patients are now seeing long-term benefits from the therapy, but we can’t stop there,” said Saul Priceman, Ph.D., associate professor in the Department of Hematology & Hematopoietic Cell Transplantation and associate director of Translational Sciences & Technologies in the T Cell Therapeutics Research Laboratories at City of Hope. “The next frontier is solid tumors, and City of Hope is taking on that challenge.” To date, City of Hope has treated more than 1,200 patients with CAR T cell therapy, either in clinical trials, which may use CARs developed by City or Hope, or Food & Drug Administration-approved CAR T cell therapies.
Targeting Advanced Cancer
The CAR T cell therapy is currently part of a first in-human Phase 1 trial at City of Hope for patients with advanced epithelial ovarian cancer who have already received platinum-based chemotherapy. The trial, led by Lorna Rodriguez-Rodriguez, M.D., Ph.D., City of Hope professor in the Division of Gynecologic Oncology, Department of Surgery, is evaluating the therapy’s safety, side effects and activity of the therapy in patients. The ovarian cancer clinical trial is currently enrolling patients for treatment.
CAR T for Solid Tumors
It’s particularly challenging to develop a CAR T cell therapy for solid tumors because the therapy needs to first reach the solid tumor and then survive in a harsh microenvironment filled with cancer cells and other cells that aim to fight off the CAR T cells. But Priceman and his team have made significant progress in overcoming these challenges.
The team’s most recent research discovered that CAR T cell therapy targeting TAG72 eradicates cancer cells in mouse models. TAG72 is an antigen found on the surface of ovarian cancer cells.
“What’s exciting about this is that TAG72 is also found on other cancer cells, including pancreatic, colorectal, breast and brain tumors, so if the clinical trial in ovarian does well, we can investigate expanding this to other patients,” Priceman added.
What Is CAR T Cell Therapy?
CAR T cell therapy involves taking a patient’s T cells, a white blood cell that helps fight disease, from the bloodstream. T cells are then reprogrammed with a CAR in a laboratory to recognize and attack a specific cancer-causing protein, such as TAG72. The reprogrammed cells are then reintroduced into the patient’s bloodstream. CAR T cells should then eradicate cancer cells. Patients are closely monitored for any side effects.
IL-12 Increases Effectiveness
Priceman and his research team also found that by adding the cytokine interleukin-12 (IL-12) — a protein that sends signals to the immune system — to the CAR T cell therapy, the treatment worked more effectively against cancer cells in the lab.
The study’s co-first authors, Eric Hee Jun Lee and John P. Murad, Ph.D., along with the rest of the team, showed that IL-12 enabled the T cells to fight the cancer and then leave the tumor region, enter the bloodstream and target other cancer cells around the body. IL-12 is not part of the current Phase 1 clinical trial, but the team plans to add it to the clinical program.
The study authors also found that delivering the CAR T cell therapy via injection where the cancer is located, regionally, is still effective in enabling CAR T cells to target cancer elsewhere. This technology allows for both improved anti-tumor activity and safety in several cancer types that have been tested to date.
“This therapy has been years in the making at City of Hope, so we are excited to finally see it in patients whose cancer is advanced and are in need of more treatments,” Priceman added.
Illustrated above: CAR T cells attack a cancer cell.