CAR T-cell therapy has produced remarkable success against blood cancers but has largely failed against solid tumors such as breast, lung, and colon cancer. One major reason is that engineered T cells cannot efficiently move through the dense tissue surrounding solid tumors.
Dr. Xue studies how cells migrate through complex physical environments. Her earlier research overturned long-standing assumptions about how cells move within living tissues and contributed to the development of CAR-macrophage approaches for solid tumors.
In this project, she will use CRISPR-based gene activation technology to systematically identify genes that improve the ability of T cells to infiltrate dense tumor tissue. Using advanced three-dimensional tumor models that closely mimic real cancers, she will screen thousands of genes to determine which ones enhance T cell movement.
Dr. Xue has already identified several promising genes that improve migration. She will now incorporate the best candidates into next-generation CAR T cells while also engineering built-in safety systems that limit activity to tumor environments. If successful, this work could overcome one of the biggest barriers facing CAR T-cell therapy and open a path toward making these treatments effective for solid tumors.
Mentor
Rogelio Hernandez-Lopez, PhD
Projects and Grants
Mapping and engineering cell-intrinsic T cell infiltration programs for enhanced solid tumor immunotherapies
