Engineering ex vivo T-cell expansion for CAR-T therapy: bridging biological fidelity and bioprocess scalability through platforms, functional consumables, and integrated closed manufacturing
- 1Anhui Provincial Key Laboratory of Infection and Immunity, School of Basic Medical Sciences Bengbu Medical University
Abstract
Background: Chimeric antigen receptor T (CAR-T) cell therapy has changed the treatment of relapsed or refractory B-cell malignancies and multiple myeloma, but manufacturing time, cost, variability, and access remain major barriers.
Scope: In this critical narrative review, we position ex vivo T-cell expansion at the interface of biological signaling and engineering design and dissect how each unit operation—from selection and activation to harvest and formulation—influences the final therapeutic product.
Key advances: Static gas-permeable culture, rocking-motion and stirred-tank bioreactors, hollow-fiber and perfusion systems, biomaterial scaffolds, microcarriers, and defined activation nanoparticles offer distinct routes to scalable expansion. Closed automated platforms now integrate multiple unit operations, while microfluidic systems, rapid manufacturing, and process analytical technologies (PAT) create new possibilities for monitoring and control, with data-driven and AI-assisted prediction emerging as supporting tools rather than established capabilities.
Challenges: Expansion remains constrained by the trade-off between cell number and preservation of memory phenotype, metabolic fitness, and potency. Donor variability, raw-material quality, consumable dependence, limited interoperability, and incomplete potency assays complicate standardization.
Outlook: Future progress will depend on coordinated development of defined raw materials, functionally designed consumables, closed-system engineering, interoperable automation, and data-driven process control. The goal is not simply to expand more cells, but to reproducibly manufacture the right cells at an acceptable cost.
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BibTeX
@article{wu2026engineering,
title = {{Engineering ex vivo T-cell expansion for CAR-T therapy: bridging biological fidelity and bioprocess scalability through platforms, functional consumables, and integrated closed manufacturing}},
author = {Qingzhi Wu and Menghui Jiang and Yuanyuan Li and Hui Huo and Haoyuan Cheng and Tian Jia and Yushu Wang and Ziwei Wang and Mengdie Ji and Jingjing Lin and Deyue Jiang and Nuo Zhang and Fuliang Chen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1981337},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1981337/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Engineering ex vivo T-cell expansion for CAR-T therapy: bridging biological fidelity and bioprocess scalability through platforms, functional consumables, and integrated closed manufacturing
AU - Qingzhi Wu
AU - Menghui Jiang
AU - Yuanyuan Li
AU - Hui Huo
AU - Haoyuan Cheng
AU - Tian Jia
AU - Yushu Wang
AU - Ziwei Wang
AU - Mengdie Ji
AU - Jingjing Lin
AU - Deyue Jiang
AU - Nuo Zhang
AU - Fuliang Chen
PY - 2026
DA - 2026/10/20
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1981337
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1981337/full
AB - Background: Chimeric antigen receptor T (CAR-T) cell therapy has changed the treatment of relapsed or refractory B-cell malignancies and multiple myeloma, but manufacturing time, cost, variability, and access remain major barriers. Scope: In this critical narrative review, we position ex vivo T-cell expansion at the interface of biological signaling and engineering design and dissect how each unit operation—from selection and activation to harvest and formulation—influences the final therapeutic product. Key advances: Static gas-permeable culture, rocking-motion and stirred-tank bioreactors, hollow-fiber and perfusion systems, biomaterial scaffolds, microcarriers, and defined activation nanoparticles offer distinct routes to scalable expansion. Closed automated platforms now integrate multiple unit operations, while microfluidic systems, rapid manufacturing, and process analytical technologies (PAT) create new possibilities for monitoring and control, with data-driven and AI-assisted prediction emerging as supporting tools rather than established capabilities. Challenges: Expansion remains constrained by the trade-off between cell number and preservation of memory phenotype, metabolic fitness, and potency. Donor variability, raw-material quality, consumable dependence, limited interoperability, and incomplete potency assays complicate standardization. Outlook: Future progress will depend on coordinated development of defined raw materials, functionally designed consumables, closed-system engineering, interoperable automation, and data-driven process control. The goal is not simply to expand more cells, but to reproducibly manufacture the right cells at an acceptable cost.
SN - 1664-3224
ER -