Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function.
Renauer P, Park J, Bai M, Acosta A, Lee W, Lin G, Zhang Y, Dai X, Wang G, Errami Y, Wu T, Clark P, Ye L, Yang Q, Chen S. Immunogenetic Metabolomics Reveals Key Enzymes That Modulate CAR T-cell Metabolism and Function. Cancer Immunology Research 2023, 11: 1068-1084. PMID: 37253111, PMCID: PMC10527769, DOI: 10.1158/2326-6066.cir-22-0565.Peer-Reviewed Original ResearchConceptsCAR T cellsHER2-specific CAR T cellsT cellsTumor microenvironmentChimeric antigen receptor T cellsT cell-based immunotherapyAntigen receptor T cellsCD19-specific chimeric antigen receptor (CAR) T cellsCAR T-cell therapyCell-based immunotherapyReceptor T cellsT-cell therapyVivo colorectal cancer modelsColorectal cancer modelT cell functionT cell metabolismTumor infiltrationEvasion mechanismsImmunosuppressive metaboliteImmune evasionCancer modelImmunologic analysisCD19-specificUnfavorable tumor microenvironmentPDK1 deficiencyIn vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy
Peng L, Renauer P, Sferruzza G, Yang L, Zou Y, Fang Z, Park J, Chow R, Zhang Y, Lin Q, Bai M, Sanchez A, Zhang Y, Lam S, Ye L, Chen S. In vivo AAV–SB-CRISPR screens of tumor-infiltrating primary NK cells identify genetic checkpoints of CAR-NK therapy. Nature Biotechnology 2024, 1-10. PMID: 38918616, DOI: 10.1038/s41587-024-02282-4.Peer-Reviewed Original ResearchPrimary NK cellsTumor-infiltrating NKCAR-NK cellsNK cellsGenetic checkpointsNatural killerChimeric antigen receptor (CAR)-NK cellsHuman primary NK cellsSolid tumor mouse modelNK cell-based immunotherapyIn vivo antitumor efficacyCAR-NK therapyNK cell therapyCell-based immunotherapyNK cell functionTumor mouse modelTumor infiltrationAntitumor efficacyCell therapyCytokine productionEnhanced cytotoxicityMouse modelSingle-cell transcriptomic landscapeClinical potentialCell function