| First Author | Ma L | Year | 2023 |
| Journal | Cell | Volume | 186 |
| Issue | 15 | Pages | 3148-3165.e20 |
| PubMed ID | 37413990 | Mgi Jnum | J:341049 |
| Mgi Id | MGI:7513730 | Doi | 10.1016/j.cell.2023.06.002 |
| Citation | Ma L, et al. (2023) Vaccine-boosted CAR T crosstalk with host immunity to reject tumors with antigen heterogeneity. Cell 186(15):3148-3165.e20 |
| abstractText | Chimeric antigen receptor (CAR) T cell therapy effectively treats human cancer, but the loss of the antigen recognized by the CAR poses a major obstacle. We found that in vivo vaccine boosting of CAR T cells triggers the engagement of the endogenous immune system to circumvent antigen-negative tumor escape. Vaccine-boosted CAR T promoted dendritic cell (DC) recruitment to tumors, increased tumor antigen uptake by DCs, and elicited the priming of endogenous anti-tumor T cells. This process was accompanied by shifts in CAR T metabolism toward oxidative phosphorylation (OXPHOS) and was critically dependent on CAR-T-derived IFN-gamma. Antigen spreading (AS) induced by vaccine-boosted CAR T enabled a proportion of complete responses even when the initial tumor was 50% CAR antigen negative, and heterogeneous tumor control was further enhanced by the genetic amplification of CAR T IFN-gamma expression. Thus, CAR-T-cell-derived IFN-gamma plays a critical role in promoting AS, and vaccine boosting provides a clinically translatable strategy to drive such responses against solid tumors. |
