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.
“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.