放疗与 CAR-T 协同治疗的全身肿瘤消退

Pancreatic ductal adenocarcinoma (PDAC) is one of the most poorly prognostic digestive tract malignancies. CLDN18. 2 CAR-T therapy has recently shown promising clinical effects in PDAC. Radiotherapy, a traditional treatment, can induce systemic immune activation and abscopal effects.

However, the synergistic effect and mechanism of their combination in PDAC treatment remain poorly understood. In this study, we developed a CLDN18. 2-specific CAR-T and applied it to unilateral and bilateral mouse tumor models.

Our results demonstrated that this synergy therapy not only improved tumor-killing effects in unilateral tumor-bearing mice but also induced regression in both local and distant tumors in bilateral tumor models.

Mechanistically, early radiation-induced apoptosis promoted the proliferation of CD8 + T cells, while increased chemokine CCL2 levels from localized and distant tumor sites facilitated CAR-T and endogenous T cell infiltration, leading to systemic tumor suppression.

This study proposes a promising approach for treating metastatic pancreatic cancer by combining radiotherapy and CAR-T therapy, elucidating the mechanism of CAR-T cell-enhanced radiotherapy effects ex vivo, and highlighting a novel strategy for combating metastatic pancreatic cancer.