NKG2D-CAR-targeted iPSC-derived MSCs efficiently target solid tumors expressing NKG2D ligand.

ABSTRACT: Mesenchymal stem cells (MSCs) hold potential in cancer therapy; however, insufficient tumor homing ability and heterogeneity limit their therapeutic benefits. Obviously, the homogeneous induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) with enhanced ability of tumor targeting could be the solution. In this study, a CAR containing the NKG2D extracellular domain was targeted at the B2M locus of iPSCs to generate NKG2D-CAR-iPSCs, which were subsequently differentiated into NKG2D-CAR-iMSCs. In vitro, NKG2D-CAR significantly enhanced migration and adhesion of iMSCs to a variety of solid tumor cells expressing NKG2D ligands. RNA sequencing (RNA-seq) revealed significant upregulation of genes related to cell adhesion, migration, and binding in NKG2D-CAR-iMS

SUBMITTER: Tang S 

PROVIDER: S-EPMC12020857 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature