Abstract
The primary challenges of CAR-T cells for solid tumor treatment involve the efficient delivery and infiltration of CAR-T cells into the tumor site, as well as overcoming the immunosuppressive tumor microenvironment. Combining chemokine-guided trafficking and delivery with the clearance of immunosuppressive barriers represents a promising strategy. An EGFR-targeted CAR-γδ T, CAR-E276 that co-expresses CCR6 and secretes PD1 blockade was in vivo validated using a non-small cell lung cancer (NSCLC) CDX model. The results from CAR-E276 indicated that integrating chemokines, checkpoint blockades, and γδ T cell properties into CAR-T cells facilitated their efficient trafficking into tumor tissues, ensured prolonged persistence, and achieved robust tumor-killing effects without inducing GvHD. Notably, CAR-E276 also exhibited potential for off-the-shelf and allogeneic applications. These findings are expected to offer valuable insights and drive the development of CAR-T therapies targeting solid tumors.