Columbia Scientists Named Chan Zuckerberg Investigators to Advance Cell Therapies
Two teams at the Vagelos College of Physicians and Surgeons received funding from the Chan Zuckerberg Biohub New York to develop next-generation, personalized cell therapies for cancer and autoimmune diseases.
Aimee Payne, chair of the Department of Dermatology, leads a project to develop cell therapies that eliminate harmful cells in patients with pemphigus, myasthenia gravis, and other autoimmune diseases.
Catherine Spina, assistant professor of radiation oncology, and Jeremy Worley, assistant professor of systems biology, lead a team that is working to adapt chimeric antigen receptor T cell (CAR T) therapy—which has shown remarkable success in treating blood cancers—for the treatment of solid tumors.
The researchers are among nine new investigators to receive funding from the Investigator Program at CZ Biohub NY. The program provides unrestricted funding to scientists, engineers, and technologists from Columbia, Rockefeller, and Yale to pursue innovative and high-impact research in systems immunology. CZ Biohub NY launched in 2023 with a mission to harness and bioengineer immune cells for the early detection, prevention, and treatment of a broad spectrum of age-related diseases.
Developing CAR T for solid cancers
The most celebrated example of cell therapy today is CAR T therapy, pioneered by Columbia’s Michel Sadelain and others for patients with leukemia and other blood cancers. In CAR T therapy, T cells are removed from the patient, genetically engineered in the lab better locate and destroy leukemic cells and infused back into the patient.
But CAR T therapy has been largely unsuccessful in treating solid tumors; the engineered cells either fail to infiltrate the tumors or the quickly exhaust themselves.
New technologies now make it possible to identify key proteins inside CAR T cells that may be holding the cells back.
Spina and Worley will use a computational method called VIPER, developed by Andrea Califano’s group at Columbia, to uncover key regulatory proteins inside cells that may govern tumor infiltration or resilience in the harsh tumor environment. The team will perturb these proteins in CAR T cells and determine if the re-engineered cells are better at infiltrating solid tumors and destroying cancer cells.
“These studies, which will test the re-engineered cells against a variety of human cancers, will provide critical proof-of-concept data needed for improving cancer immunotherapy outcomes,” Spina says.
Cell therapy for autoimmune diseases
Nearly one in 10 people in the U.S. have an autoimmune disease, which occurs when the body’s immune system mistakenly attacks healthy tissues.
Current therapies suppress the entire immune system, leaving patients vulnerable to potentially fatal infections.
Payne has developed chimeric autoantibody receptor T cell (CAAR T) therapy, a spinoff of CAR T therapy, that is designed to direct therapeutic cells to attack the autoimmune cells that cause the disease and leave healthy immune cells alone.
CAAR T therapy is being tested across the country in patients with a type of myasthenia gravis caused by autoimmune cells that attack a protein on muscle cells called muscle-specific tyrosine kinase (MuSK). The condition leads to muscle weakness and potentially life-threatening respiratory emergencies.
Early data from the first-in-human trial of CAAR T therapy suggests that the engineered cells expand and persist in patients and is associated with clinical improvements, although some participants have experienced serious side effects. Payne’s team will evaluate each patient to understand how MuSK-CAART influences individual immune responses.
“As the first highly targeted precision cellular immunotherapy to enter clinical trials for autoimmunity, CAAR T gives us an opportunity to study how this method of immune engineering functions within autoimmune disease patients. Pairing this knowledge with our experience using CAR T for the treatment of B cell cancers will help us identify strategies for improving the design of precision cellular immunotherapies for myasthenia gravis and other autoimmune diseases,” Payne says.