Universal CAR-T cell therapy: overcoming key hurdles on the path to off-the-shelf adoption.
4 affiliations
- 1Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
- 2State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai, China.
- 3Engineering Research Center of Cell & Therapeutic Antibody, MOE, School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
- 4Department of Gynaecology and Obstetrics, Shanghai Pudong New Area people's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract
Chimeric antigen receptor (CAR) T cells have revolutionized oncology, delivering unprecedented clinical responses in patients with refractory B-cell malignancies. However, the traditional autologous paradigm - encompassing patient-specific leukapheresis, genetic modification, and extensive ex vivo expansion - imposes severe constraints on manufacturing timelines, costs, and global scalability. Allogeneic universal CAR-T (uCAR-T) reimagines this therapeutic unit as an "off-the-shelf" cellular medicine, utilizing healthy donor-derived cells produced in standardized batches to overcome the bottlenecks of individualized therapy. Over the past decade, the field has transitioned from foundational proof-of-concept studies in murine models to sophisticated early-phase human clinical trials. This review delineates the core biological and engineering principles of uCAR-T, specifically focusing on the genomic strategies employed to mitigate graft-versus-host disease (GvHD) and host-versus-graft disease (HvGD). We synthesize pivotal preclinical and clinical data alongside a comprehensive overview of the current clinical landscape. Furthermore, we highlight the primary translational hurdles remaining: ensuring durable CAR-T persistence and navigating the complexities of innate and adaptive immune rejection. We explore the potential for combination immunotherapies and specialized CAR architectures designed to penetrate solid tumors. Ultimately, uCAR-T is poised to democratize cellular immunotherapy, offering a scalable and transformative therapeutic perspective across diverse disease indications.
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BibTeX
@article{liu2026universal,
title = {{Universal CAR-T cell therapy: overcoming key hurdles on the path to off-the-shelf adoption.}},
author = {Zibo Liu and Zhongyao Cai and Junshi Zhang and Xinran Yu and Xuanming Yang},
journal = {Medical review (2021)},
year = {2026},
month = jun,
doi = {10.1515/mr-2026-0017},
url = {https://europepmc.org/article/MED/42924291},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Universal CAR-T cell therapy: overcoming key hurdles on the path to off-the-shelf adoption.
AU - Zibo Liu
AU - Zhongyao Cai
AU - Junshi Zhang
AU - Xinran Yu
AU - Xuanming Yang
PY - 2026
DA - 2026/06/01
JO - Medical review (2021)
DO - 10.1515/mr-2026-0017
UR - https://europepmc.org/article/MED/42924291
AB - Chimeric antigen receptor (CAR) T cells have revolutionized oncology, delivering unprecedented clinical responses in patients with refractory B-cell malignancies. However, the traditional autologous paradigm - encompassing patient-specific leukapheresis, genetic modification, and extensive ex vivo expansion - imposes severe constraints on manufacturing timelines, costs, and global scalability. Allogeneic universal CAR-T (uCAR-T) reimagines this therapeutic unit as an "off-the-shelf" cellular medicine, utilizing healthy donor-derived cells produced in standardized batches to overcome the bottlenecks of individualized therapy. Over the past decade, the field has transitioned from foundational proof-of-concept studies in murine models to sophisticated early-phase human clinical trials. This review delineates the core biological and engineering principles of uCAR-T, specifically focusing on the genomic strategies employed to mitigate graft-versus-host disease (GvHD) and host-versus-graft disease (HvGD). We synthesize pivotal preclinical and clinical data alongside a comprehensive overview of the current clinical landscape. Furthermore, we highlight the primary translational hurdles remaining: ensuring durable CAR-T persistence and navigating the complexities of innate and adaptive immune rejection. We explore the potential for combination immunotherapies and specialized CAR architectures designed to penetrate solid tumors. Ultimately, uCAR-T is poised to democratize cellular immunotherapy, offering a scalable and transformative therapeutic perspective across diverse disease indications.
SN - 2097-0773
SN - 2749-9642
ER -