Figure 7.

The trifecta of successful chimeric antigen receptor (CAR) T cell therapies in solid tumors. The ultimate CAR T cell therapy has tumor specificity, potent migratory capacity and persistence, and improves the host immune response. (A) Bispecificity through syn-Notch technology augments targeting to tumor/tumor-specific tissue. (B) Engineering a T cell with enhanced persistence and migratory capacity—such as a Th17 or CD4⁺CD26^high cell—or with self-renewing properties—such as a CD8⁺ T_SCM cell—will enhance long-term memory responses to prevent tumor recurrence. (C) Secretion of PD-1 blockade and cytokines such as IL-12, IL-15, IL-18, or IL-21 locally could overcome the suppressive tumor microenvironment, reinvigorate the exhausted host immune response to other tumor antigens, and synergize with CAR-specific T cells to destroy large heterogenous solid tumors.