The W. M. Keck Foundation has awarded a Medical Research Grant to Dr. Roarke Kamber, a member of the Bakar Aging Research Institute (BARI) at UCSF, to develop a platform for reprogramming non-immune cells to recognize and destroy cancer. The grant is one of twelve Medical Research Awards in the Foundation's most recent funding cycle. As diseases like cancer become increasingly prevalent with age, Dr. Kamber’s project is closely aligned with BARI’s mission to decode the biology of aging and develop interventions that promote healthy longevity.
The W. M. Keck Foundation, established in 1954 by William Myron Keck, has a storied history of fueling transformative discoveries. Born out of Keck's vision to give back to society through philanthropy, the foundation initially focused on supporting education and community initiatives but evolved to emphasize high-risk, high-reward research in science, engineering, and medicine. Over the decades, it has awarded over 7,500 grants totaling more than $2.2 billion. What sets the Keck Foundation apart is its commitment to funding bold ideas that challenge conventional paradigms, projects often deemed too new or speculative for traditional federal grants.
Dr. Kamber's project aims to broadly expand the range of cell types that can be engineered to kill cancer cells. In recent years, researchers have equipped several immune cell types with chimeric antigen receptors, or CARs, that improve their capacity to target and destroy cancer cells. However, many of the most lethal tumors grow in tissues where immune cells are scarce or excluded, limiting the reach of current immunotherapies. This problem is compounded in older patients, where immune function naturally declines with age. Kamber’s project proposes a creative solution to this problem by creating CARs that endow non-immune cells, which are not excluded from tumors, with the ability to kill cancer cells.
“Non-immune cells have an underappreciated, latent capacity to phagocytose (or eat) other cells, perhaps because the ancestor of all animal cells was likely a phagocytic, amoeba-like organism,” said Kamber. “We have been testing whether we can ‘awaken’ this capacity and redirect it towards cancer cells, by extending synthetic biology tools similar to those that powered the CAR-T cell therapy revolution.” The Keck-funded work will uncover the molecular pathways that control cancer killing by non-immune cells, screen libraries of synthetic receptor designs to optimize CAR architectures for different cell types, and evaluate the most promising constructs in mouse cancer models using adeno-associated virus (AAV) delivery. This work is particularly relevant to aging research, as immune dysfunction and chronic inflammation (two hallmarks of aging), often enable cancer progression. By rewiring resident non-immune cells to act as sentinels, Kamber’s work could enable a new frontline defense against age-associated cancers, potentially reducing reliance on systemic immunotherapies that may falter in elderly patients. The platform's broader applications extend to other diseases characterized by immune exclusion, such as neurodegenerative and fibrotic diseases, opening doors to novel interventions in geroscience.
For this effort, Kamber will work with a team of expert collaborators at UCSF, including Wendell Lim, PhD, Byers Distinguished Professor of Cellular and Molecular Pharmacology and Director of the UCSF Cell Design Institute; Michael McManus, PhD, Professor of Microbiology and Immunology; Holger Willenbring, MD, PhD, Professor of Surgery and Director of the UCSF Liver Center; and Saul Villeda, PhD, Associate Professor of Anatomy and Associate Director of BARI. Together, the team brings expertise spanning synthetic receptor engineering, functional genomics, in vivo gene delivery, and the biology of aging and regeneration.
BARI Director Leanne Jones, PhD, highlighted the project's alignment with BARI's goals: "Dr. Kamber's innovative CAR-X platform exemplifies the bold, interdisciplinary science that defines BARI. As we unravel the complexities of aging, addressing how immune decline fuels diseases like cancer is paramount. This Keck award not only supports his groundbreaking work but also reinforces our commitment to fostering research that bridges fundamental immunology, bioengineering, and geroscience. We're thrilled to see one of our members leading this charge toward healthier aging."
This accolade underscores BARI's growing influence in the field of aging research. Founded to unite UCSF's expertise across campuses, from the Fein Memory and Aging Center to the Division of Geriatrics, BARI tackles intractable questions in geroscience through collaborative efforts. With members like Dr. Kamber pushing boundaries, the institute continues to drive discoveries that could extend healthspan and combat age-related diseases. As we celebrate this milestone, it's a reminder of the power of philanthropic support for high-risk, high-reward innovative science like that from the W. M. Keck Foundation. By betting on unconventional ideas, they enable leaps that federal funding might overlook. For BARI, this award is more than recognition—it's fuel for future innovations that promise a vibrant, disease-free later life for all.
About the W. M. Keck Foundation
The W. M. Keck Foundation was established in 1954 in Los Angeles by William Myron Keck, founder of The Superior Oil Company. One of the nation's largest philanthropic organizations, the W. M. Keck Foundation supports outstanding science, engineering and medical research. The Foundation also supports undergraduate education and maintains a program within Southern California to support arts and culture, education, health and community service projects.