In a new cell-culture and mouse-model study, a research team at the McKnight Brain Institute led by UF’s Jianping Huang, M.D., Ph.D., and Linchun Jin, M.D., Ph.D., demonstrated a novel technique using the injection of genetically modified cells to enhance the effectiveness of immunotherapy to halt or even shrink late-stage solid tumors.
In the study, published in Nature Communications, investigators aimed to tackle the main obstacles of using chimeric antigen receptor (CAR T-cell therapy) to target large tumors such as glioblastoma, ovarian cancer or pancreatic cancer. In aggressive cancers, the ability to treat late-stage tumors that can’t be surgically removed is potentially lifesaving.
The team used treatment-resistant tumor models to demonstrate that utilizing modified cells may reverse immunosuppression induced by a tumor, thereby halting tumor growth. The investigators co-opted the release of a tiny protein molecule called interleukin-8 (IL-8) from tumors to enhance T-cell movement. This markedly boosted migration and persistence of T-cells within the tumor, inducing a complete regression of the tumors in a rodent model and yielding long-term protection.
The study lays the foundation for a human clinical trial testing the technique in glioblastoma.
“These findings address the significant obstacle of getting enough activated CAR T cells into the microenvironment of solid tumors where they can induce the regression of large tumors,” said Duane Mitchell, M.D., Ph.D., director of UF’s Preston A. Wells Jr. Center for Brain Tumor Therapy and vice chair of research for the Lillian S. Wells Department of Neurosurgery. “Dr. Huang is working with the translational research teams at our Wells Center, UF Health Cancer Center and Powell Cell and Gene Therapy Center to advance this novel CAR T cell therapy into clinical trials.”
“This study furthers our continued efforts to develop innovative therapies with a potent antitumor response for patients with glioblastoma and other cancers, and our approach will help to improve therapeutic efficacy for other CAR T cell therapies in solid tumors, ” said Huang.
This research is supported by the Adam Michael Rosen Foundation, Inc.; the Wells Endowment; the Florida Center for Brain Tumor Research; Accelerate Brain Cancer Cure; and the UF Health Cancer Center/Wells Brain Tumor Center Pilot Award.