(A) Multiplex immunofluorescent staining of a human lung adenocarcinoma that demonstrates heterogeneous antigen expression of MSLN and MUC16 on tumor cells. (B) Addressing TAA heterogeneity in solid tumors: (1) Single TAA-targeted CAR T-cell therapy may result in antigen escape or the outgrowth of tumor cells that either express very low levels of TAA (below CAR T-cell activation threshold) or do not express the targeted TAA. Targeting two TAAs simultaneously, either by co-administration of CAR T cells targeting different antigens (2) or using a TanCAR (3), can mitigate tumor escape. A broad spectrum of TAAs can be targeted simultaneously with switchable CAR-transduced T cells (4).
CAR, chimeric antigen receptor; MSLN, mesothelin; MUC16, mucin 16; TAA, tumor-associated antigen; TanCAR, tandem CAR