Jeffrey Ravetch, Rockefeller University - Dendritic Cells

We’re in need of new ways to fight cancer.Jeffrey Ravetch, Theresa and Eugene M. Lang professor of immunology, virology, and microbiology at the Rockefeller University, examines one new path forward.Ravetch is a faculty member in the David Rockefeller Graduate Program, and the Tri-Institutional M.D.-Ph.D. ProgramWhile cancer immunotherapy has helped many patients, most do not respond—and those who do often face serious side effects. In my lab, we’re working to make immunotherapy both safer and more effective by targeting a key part of the immune system: dendritic cells.Dendritic cells are the body’s sentinels. They detect threats like infections or tumors and activate other immune cells to fight back. But tumor cells fight back too—by creating an environment that suppresses the immune response. Most current immunotherapies try to remove this suppression, like taking the foot off the brakes. Our approach is different: we aim to press the accelerator.We focus on a protein called CD40, found on dendritic cells, which powerfully stimulates immune activity. But previous attempts to target CD40 systemically have failed—causing limited immune activation and significant side effects.To address this, we developed a new antibody, 2141-V11, designed to strongly activate dendritic cells—but only within the tumor itself. We then launched a first-in-human clinical trial at The Rockefeller University Hospital. Patients with cancers like metastatic melanoma and breast cancer received direct injections into a single tumor site.The results were remarkable. The treatment was safe, and repeated doses led to dramatic responses—even complete tumor disappearance in some patients. Not only did the injected tumors shrink, but distant metastases also vanished. Biopsies showed no cancer cells—just organized immune structures resembling lymph nodes.This suggests that local CD40 stimulation can spark a body-wide immune response—strong enough to clear tumors but precise enough to spare healthy tissue.We’re now expanding trials into bladder, prostate, and brain cancers—and testing combination therapies to help more patients benefit from this promising new approach. This is a public episode. If you would like to discuss this with other subscribers or get access to bonus episodes, visit www.academicminute.org