Dual-specific T cells, expressing a Her2-specific chimeric antigen receptor (CAR) and a gp100-specific TCR, were generated using genetic modification. Adoptive transfer of dual-specific T cells, combined with an injection of a gp100-expressing vaccinia virus vaccine, eradicated a variety of large syngeneic mouse tumours, including E0771-Her2 breast tumors (Slaney et al, 2017). However, some tumors, including AT3-Her2 breast tumors, do not respond completely. Therefore, E0771-Her2 and AT3-Her2 provided an opportunity to define elements of susceptibility and resistance to therapy. Using immunohistochemistry, we demonstrated a mixed nature of AT3-Her2 tumors composed of islands of round tumor cells amidst streams of spindle-shaped tumor cells and stroma. Whereas infiltration of adoptively transferred dual-specific T cells was robust and evenly distributed in E0771-Her2 tumors, T cells localized to areas of spindle-shaped cells and were largely excluded from AT3-Her2 tumor islands. In addition, using in vitro cytotoxicity assays, AT3-Her2 cells were demonstrated to be relatively resistant to both perforin- and TNF-mediated killing. In ongoing experiments, we seek to enhance the abilities of dual-specific T cells to infiltrate tumors and kill malignant cells. Addressing these parameters may enable the extension of this therapy to a broader range of tumours and lead to the design of new immunotherapy regimens for the treatment of cancer patients.