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. 2022 Aug 15;132(16):e162322. doi: 10.1172/JCI162322

Figure 1. BiCisCAR T cells have enhanced efficacy against solid tumors.

Figure 1

(A) Single target CAR T cells recognize and kill cancer cells expressing their target antigen. However, tumor cells that do not express or downregulate the targeted antigen are resistant to killing by CAR T cells and proliferate. Chronic antigen persistence exhausts the single target CAR T cells as well as endogenous CD8+ T cells and prevents differentiation of a central memory endogenous T cell pool. (B) BiCisCAR T cells secrete increased levels of cytokines compared with single target CAR T cells. These cytokines can promote chemotaxis of inflammatory cells from the bone marrow. BiCisCAR T cells also promote apoptosis with antigen spilling and a robust local immune response. Antigen presenting cells (APCs) activate at the tumor site and migrate to the lymph nodes to prime endogenous T cells. BiCisCAR T cells with low checkpoint expression stimulate an expanded endogenous T cell response, which persists as central memory T cells, enabling tumor control.