iPSC-Derived T and CAR-T Cells of Distinct Phenotypes: Current Protocols, Challenges and Potential for Cancer Treatment
- 1Research Centre for Medical Genetics, 1 Moskvorechye St., Moscow 115522, Russia
Abstract
Adoptive T-cell therapy has demonstrated substantial clinical efficacy in several hematological malignancies, but autologous manufacturing remains limited by variability in starting cell material, manufacturing time, product heterogeneity, and T-cell dysfunction. Induced pluripotent stem cells (iPSCs) provide a potentially scalable and genetically engineerable source for the generation of standardized allogeneic T-cell products. This review summarizes current approaches to the differentiation of iPSCs into distinct T-cell phenotypes and evaluates their potential for cancer immunotherapy. We first discuss iPSC-derived conventional αβ T cells, including recent advances in feeder-free and scalable differentiation, maturation, and genetic engineering, as well as preclinical and early clinical evidence. We then examine γδ T cells, invariant natural killer T cells, and mucosal-associated invariant T cells, focusing on their distinctive antigen-recognition mechanisms, effector functions, tissue tropism, differentiation strategies, and therapeutic applications. Across these populations, iPSC technology may facilitate standardized and scalable production while enabling targeted engineering of T-cell specificity and functional properties. However, important challenges remain, including efficient lineage-specific differentiation, maturation, phenotypic consistency, long-term persistence, tumor infiltration, and control of alloreactivity and immunogenicity. Overall, iPSC-derived T cells represent a versatile platform for developing diverse cellular immunotherapies, although their clinical potential remains dependent on further technological and translational advances.
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BibTeX
@article{maiak2026ipscderived,
title = {{iPSC-Derived T and CAR-T Cells of Distinct Phenotypes: Current Protocols, Challenges and Potential for Cancer Treatment}},
author = {Margarita Maiak and Anna Efremova and Tatiana Budagova and Diana Mokrousova and Dmitry Goldshtein},
journal = {Cells},
year = {2026},
month = oct,
doi = {10.3390/cells15211938},
url = {https://www.mdpi.com/2073-4409/15/21/1938},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - iPSC-Derived T and CAR-T Cells of Distinct Phenotypes: Current Protocols, Challenges and Potential for Cancer Treatment
AU - Margarita Maiak
AU - Anna Efremova
AU - Tatiana Budagova
AU - Diana Mokrousova
AU - Dmitry Goldshtein
PY - 2026
DA - 2026/10/25
JO - Cells
DO - 10.3390/cells15211938
UR - https://www.mdpi.com/2073-4409/15/21/1938
AB - Adoptive T-cell therapy has demonstrated substantial clinical efficacy in several hematological malignancies, but autologous manufacturing remains limited by variability in starting cell material, manufacturing time, product heterogeneity, and T-cell dysfunction. Induced pluripotent stem cells (iPSCs) provide a potentially scalable and genetically engineerable source for the generation of standardized allogeneic T-cell products. This review summarizes current approaches to the differentiation of iPSCs into distinct T-cell phenotypes and evaluates their potential for cancer immunotherapy. We first discuss iPSC-derived conventional αβ T cells, including recent advances in feeder-free and scalable differentiation, maturation, and genetic engineering, as well as preclinical and early clinical evidence. We then examine γδ T cells, invariant natural killer T cells, and mucosal-associated invariant T cells, focusing on their distinctive antigen-recognition mechanisms, effector functions, tissue tropism, differentiation strategies, and therapeutic applications. Across these populations, iPSC technology may facilitate standardized and scalable production while enabling targeted engineering of T-cell specificity and functional properties. However, important challenges remain, including efficient lineage-specific differentiation, maturation, phenotypic consistency, long-term persistence, tumor infiltration, and control of alloreactivity and immunogenicity. Overall, iPSC-derived T cells represent a versatile platform for developing diverse cellular immunotherapies, although their clinical potential remains dependent on further technological and translational advances.
SN - 2073-4409
ER -