ERBB2 and neoplasm: Our results indicate that this plays a crucial role particularly in the context of an ECM embedded 3D tumor microenvironment: i.e., even though a high affinity bsAb recognizing a membrane distal HER2 epitope i) supports T-cell mediated killing of tumor cells in 2D co-culture and ii) readily concentrates in an ECM embedded tumoroid; it fails to promote active recruitment of T-cells and subsequent T-cell mediated tumoroid destruction, and this cannot be compensated for by increasing bsAb concentrations.