Adoptive Cell Transfer Incorporating Vaccination (ACTIV) therapy is a promising strategy to enhance CAR T cell therapy of solid cancers. In ACTIV therapy dual-specific T cells, expressing a Her2-specific CAR and a TCR specific for gp100, are combined with an injection of a gp100-expressing vaccinia virus vaccine. ACTIV therapy can lead to the eradication of a variety of large syngeneic mouse tumours, including E0771-Her2 breast tumours (Slaney et al, 2017). However, some tumours, including AT3-Her2 breast tumours, 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 that AT3-Her2 tumours were composed of islands of round tumour cells amidst streams of spindle-shaped stromal cells. Whereas infiltration of adoptively transferred dual-specific T cells was robust and evenly distributed in E0771-Her2 tumours, T cells localized to areas of spindle-shaped cells and were largely excluded from AT3-Her2 tumour 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 tumours and kill malignant cells. In addition, AT3-Her2 differed metabolically from E0771-Her2, with AT3-Her2 having higher levels of oxidative phosphorylation. 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.