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Autocrine PD-1-Blocking Nanobodies Enhance the Antitumor Efficacy of TCR-Like CAR-T Cells by Attenuating T Cell Exhaustion

ABSTRACT: This study investigates a next-generation TCR-mimic (TCRm) chimeric antigen receptor T (CAR-T) cell platform engineered to overcome two major obstacles in solid tumor immunotherapy: intracellular tumor-associated antigen targeting and PD-1/PD-L1-mediated T cell exhaustion. We developed WT1-CAR-Nb T cells, which co-express a TCRm CAR specific for the WT1 peptide/HLA-A*02:01 complex and a constitutively secreted high-affinity anti-PD-1 nanobody. The transcriptomic dataset submitted here was generated to characterize the molecular signatures associated with enhanced functional durability conferred by autocrine PD-1 blockade. Specifically, RNA sequencing was performed on WT1-CAR-Nb T cells versus conventional WT1-CAR T cells following chronic antigen stimulation in vitro, aiming to delineate the differentially expressed genes and enriched pathways underpinning the attenuated exhaustion phenotype, preserved stem-like memory properties, and pro-survival transcriptional program of WT1-CAR-Nb T cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE329992 | GEO | 2026/09/23

REPOSITORIES: GEO

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