嵌合抗原受体细胞作为实体瘤治疗中 TNFα 局部递送的工具

Chimeric antigen receptor (CAR)-T cells are effective in treating blood cancers but not solid cancers and can cause severe side effects, including cytokine release syndrome (CRS). One strategy to enhance the efficacy of CAR-T cells while avoiding CRS in cancer treatment is to deliver a single tumoricidal factor.

TNF is well known for triggering apoptosis signaling; however, it alone is not effective in treating cancers because it significantly increases the levels of inhibitor of apoptosis proteins (IAPs), a family of E3 ubiquitin ligases that block caspase-induced apoptosis.

Thus, localized delivery of TNF by targeting the tumors using the adoptive cells combined with an IAP antagonist, which degrades IAP proteins, could lead to improved outcomes in cancer treatment. This article reviews TNF -induced apoptosis signaling pathway, outlines the principles for designing CAR-T cells, CAR-macrophages and CAR-dendritic cells expressing TNF , used alone or in combination with IAP antagonists, and discusses the potential contraindications of IAP antagonists with several clinical used drugs for cancer treatment.