Extended Data Fig. 10: Modelling of anticipated outcomes after single or combinatorial CAR T cell treatment schemas.
From: CAR T cell trogocytosis and cooperative killing regulate tumour antigen escape
a–h, Antigen-positive relapse (a–d) versus tumour control scenarios (e–h) after single or combinatorial CAR T cell targeting. a, Antigen high relapse of residual tumour cells in the absence of CAR T cells. b, Antigen-low relapse in the presence of insensitive or exhausted CAR T cells. c, Tumour relapse after sequential combinatorial targeting failing against tumour cells with low antigen densities. Tumour rejection could overcome the relapse scenarios (a–c) by achieving a higher effector:target ratio (e–g), after higher T cell dose infusion or greater post-infusion expansion, operating through additive or cooperative tumour elimination. In d and h, combinatorial targeting is mediated by dual-targeted CAR T cells, which may still fail in the face of low antigen densities (d) depending on the co-stimulatory combinations (h). In all cases, low antigen density may be either constitutively low or actively lowered after CAR T cell-mediated trogocytosis. Antigen-negative escapes are not represented. Other, yet undiscovered, escape mechanisms may exist.
