Genetic engineering and allogeneic optimization of Vδ1 γδ CAR-T cells (ADI-270) for cancer immunotherapy
Year: 2025
Type: article
Abstract: Genetic engineering has fundamentally transformed T cell–based therapies by enabling tumor targeting capability, improving their functionality, and facilitating allogeneic use. These strategies—originally developed in αβ chimeric antigen receptor (CAR)-T cells—have become increasingly established as blueprints for enhancing the function of other immune effector cells, including gamma delta (γδ) T cells. A recent study by Nishimoto et al showcased the adaptation of these engineering approaches to Vδ1 γδ T cells (ADI-270) by coexpressing a CD70-targeted CAR and a dominant-negative TGFβRII receptor (dnTGFβRII) to target CD70 + malignancies, addressing immunosuppression and host-versus-graft rejection. This commentary explores αβ T cell-derived engineering strategies applicable to γδ T cells, while also highlighting genome-editing innovations poised to advance next-generation γδ CAR-T development.
Institutions: University of Minnesota, Masonic Cancer Center
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,490
Funders: U.S. Department of Defense, Children's Cancer Research Fund, CURE Childhood Cancer, Fanconi Anemia Research Fund, Randy Shaver Cancer Research and Community Fund, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, Center for Scientific Review, Congressionally Directed Medical Research Programs
Awards: G1005149074, G1345980661, G1442899210, G1643994854, Targeting Pediatric Solid Tumors with Multiplex Edited, Dual CAR Gamma Delta T Cells, G2976084676, G3401702990, G3829142046, G4210313847, G4419096236, G4690314899, G4862120073, G5126897235, G5304273042, G6159438681, Allogeneic, Multiplex Base-Edited, Dual-Targeted Gamma Delta CAR-T Cell Development for Metastatic Castration-Resistant Prostate Cancer, G6433449787, G7099872298, Engineered B Cells as a Universal Platform for the Treatment of Enzymopathies, G8493443750, Characterization and In Vivo Gene Therapy Using a Novel Fanconi Anemia Mouse Model of Bone Marrow Failure, G9000052278, G9000124846, G9000167443, G9000180936, G9000249913, G9000271504, Integrated Immune Engineering for Poor Prognosis Cancers, Center for Multiparametric Imaging of Tumor Immune Microenvironments, G982310095
OpenAlex ID: W7117310018