CAR T-cell therapy has shown remarkable success in treating blood cancers, but its effectiveness in solid tumors has been more limited. A key contributing factor is that in solid cancers, like breast and pancreatic cancer, the extracellular matrix (ECM) that surrounds cells and tissues is often dysregulated, forming a barrier that blocks immune cells from reaching and killing cancer cells. Dr. Manish Ayushman’s research aims to transform the ECM from a barrier into a therapeutic ally. His approach is three-fold: 1) engineer cytokines that bind the tumor ECM for sustained immune activation, 2) design ECM-targeting receptors to anchor CAR T cells inside the tumor, and 3) enable CAR T cells to break down the ECM to improve infiltration. These approaches could work individually or in combination with other drugs to help immune cells persist and function more effectively in solid tumors. “I want to transform the tumor ECM from a barrier into a scaffold for CAR T-cell therapy,” Dr. Ayushman explains. If successful, his work could significantly boost the success of cell therapies for some of the toughest cancers.

Trained in chemical- and bio-engineering, Dr. Ayushman has long explored how physical properties of tissues, like stiffness or elasticity, shape cell behavior. His doctoral work uncovered how subtle, local mechanics in engineered hydrogels can influence stem cell fate and disease responses. Now, he’s applying that insight to cancer: developing biomaterials that reveal how tumors resist therapy and how we can fight back.

Sponsor

Wendell Lim, PhD

Research Focus

CAR T-cell therapy, solid tumors, tumor infiltration

Projects and Grants

Programming cell therapies that locally remodel the tumor extracellular matrix to improve efficacy against solid tumors