LOS ANGELES, CA — Researchers at City of Hope recently published preclinical research in 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, PhD, 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.”
The therapy is currently in 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, MD, PhD, City of Hope professor in its Division of Gynecologic Oncology, Department of Surgery, is testing the therapy’s safety, side effects, and activity of the therapy in patients. The trial is currently enrolling patients for treatment.
Challenges of developing CAR T-cell therapy for solid tumors
Developing a CAR T cell therapy for solid tumors is particularly challenging because the therapy needs to first reach the solid tumor and then survive in a harsh microenvironment that is filled with cancer cells and other cells that prevent attack by the CAR T cells. But Priceman and team have made significant progress in overcoming these challenges.
The team’s most recent research found that a CAR T cell therapy targeting tumor-associated glycoprotein-72 (TAG-72)—a target found on the surface of ovarian cancer cells—eradicates cancer cells in mouse models.
“What’s exciting about this is that TAG-72 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,” said Priceman.
CAR T cell therapy involves taking a patient’s T cells, reprogramming them with a CAR to recognize and attack a specific cancer-causing protein (such as TAG-72), and reintroducing them into the patient’s bloodstream. CAR T cells should then eradicate cancer cells. Patients are closely monitored for any side effects.
Effect of IL-12 on CAR T-cell therapy
Priceman and his team also found that by adding the cytokine, interleukin-12 (IL-12), to the CAR T-cell therapy, the treatment worked more effectively against cancer cells in the lab. The co-first authors, Eric Hee Jun Lee, BA, and John P. Murad, PhD, along with the rest of the team, showed that IL-12 also enabled the T cells to both fight cancer and leave the tumor area, enter the bloodstream and target other cancer cells around the body. Priceman noted that IL-12 is not currently part of the current Phase 1 clinical trial.
The preclinical research also found that delivering the CAR T cell therapy via an injection, local to the cancer, is also effective in enabling CAR T cells to target cancer elsewhere. This technology allows for both safety and improved antitumor activity in several cancer types tested to date.
- This press release was originally published on the City of Hope website