Synthetic NKG2D receptor (SNR) armored CAR-T cells overcome antigen heterogeneity of solid tumor.

ABSTRACT:

Background

CAR-T cell therapy has demonstrated remarkable success in hematologic malignancies; however, its effectiveness against solid tumors remains limited due to tumor antigen heterogeneity. NKG2DLs, including MICA/B and the ULBP family, are stress-induced molecules frequently upregulated on the surface of tumor cells and components of the tumor microenvironment, providing attractive targets for immunotherapy. To broaden the targeting capability beyond conventional Claudin18.2-directed CAR-T cells, we engineered a Synthetic NKG2D Receptor (SNR). The SNR comprises the extracellular domain of NKG2D fused with the intracellular signaling domains of DAP10 and DAP12, enabling effective targeting of NKG2D ligands (NKG2DLs).

Methods

Expression of NKG2DLs and CLDN18.2 were detec

SUBMITTER: Sun M 

PROVIDER: S-EPMC12528229 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature