Allogeneic CAR-T, CAR-NK, and in vivo CAR-T for immune-mediated inflammatory diseases: comparative evidence, platform trade-offs, and translational challenges
4 affiliations
- 1Department of Rheumatology and Immunology, The Fifth Affiliated Hospital, Sun Yat-Sen University
- 2Department of Research and Development, Antengene Corporation
- 3School of Public Health (Shenzhen), Sun Yat-Sen University
- 4Department of Rheumatology and Immunology, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China
Abstract
Immune-mediated inflammatory diseases (IMIDs) remain treatment-dependent in many patients with severe, refractory, or organ-threatening disease. Deep B-cell depletion using chimeric antigen receptor (CAR)-based therapies may induce clinical improvement and measurable immune reconstitution, but conventional autologous CAR-T manufacturing limits speed, standardization, and access. This structured narrative review compares allogeneic CAR-T, allogeneic CAR-natural killer (CAR-NK), and in vivo CAR-T. Bibliographic databases, trial registries, conference repositories, reference lists, and traceable sponsor, media, and regulatory sources were searched through 3 September 2026. Allogeneic CAR-T has the broadest clinical evidence base, although cohorts are small and mostly early-phase. All CAR-NK products with reported IMID clinical data are allogeneic; available studies suggest transient kinetics, repeat-infusion feasibility, and encouraging short-term tolerability, but durability is uncertain. Peer-reviewed in vivo evidence now includes a five-patient non-integrating LNP/linear mRNA report and a 16-patient integrating lentiviral report. Both are early, uncontrolled studies and neither supports class-wide inference. Disease-specific outcomes, background treatment, follow-up, and assays differ markedly. Complete treatment-free remission was distinguished from glucocorticoid withdrawal, immunosuppressant reduction, and remission on permitted therapy. CAR-cell, transgene DNA, and RNA detection were not pooled, and peripheral blood B-cell depletion was not treated as proof of tissue depletion. Naive-dominant B-cell recovery and declining autoantibodies indicate immune remodeling, not restored tolerance. No indirect efficacy ranking is justified. Prospective studies need standardized disease endpoints, treatment-free remission definitions, analyte-specific pharmacokinetics, paired blood–tissue pharmacodynamics, and long-term genomic, immune, and safety surveillance.
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BibTeX
@article{liang2026allogeneic,
title = {{Allogeneic CAR-T, CAR-NK, and in vivo CAR-T for immune-mediated inflammatory diseases: comparative evidence, platform trade-offs, and translational challenges}},
author = {Zhenguo Liang and Mengyun Mao and Hui Xie and Yuhan Xing and Dongze Wu},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1931185},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931185/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Allogeneic CAR-T, CAR-NK, and in vivo CAR-T for immune-mediated inflammatory diseases: comparative evidence, platform trade-offs, and translational challenges
AU - Zhenguo Liang
AU - Mengyun Mao
AU - Hui Xie
AU - Yuhan Xing
AU - Dongze Wu
PY - 2026
DA - 2026/10/28
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1931185
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1931185/full
AB - Immune-mediated inflammatory diseases (IMIDs) remain treatment-dependent in many patients with severe, refractory, or organ-threatening disease. Deep B-cell depletion using chimeric antigen receptor (CAR)-based therapies may induce clinical improvement and measurable immune reconstitution, but conventional autologous CAR-T manufacturing limits speed, standardization, and access. This structured narrative review compares allogeneic CAR-T, allogeneic CAR-natural killer (CAR-NK), and in vivo CAR-T. Bibliographic databases, trial registries, conference repositories, reference lists, and traceable sponsor, media, and regulatory sources were searched through 3 September 2026. Allogeneic CAR-T has the broadest clinical evidence base, although cohorts are small and mostly early-phase. All CAR-NK products with reported IMID clinical data are allogeneic; available studies suggest transient kinetics, repeat-infusion feasibility, and encouraging short-term tolerability, but durability is uncertain. Peer-reviewed in vivo evidence now includes a five-patient non-integrating LNP/linear mRNA report and a 16-patient integrating lentiviral report. Both are early, uncontrolled studies and neither supports class-wide inference. Disease-specific outcomes, background treatment, follow-up, and assays differ markedly. Complete treatment-free remission was distinguished from glucocorticoid withdrawal, immunosuppressant reduction, and remission on permitted therapy. CAR-cell, transgene DNA, and RNA detection were not pooled, and peripheral blood B-cell depletion was not treated as proof of tissue depletion. Naive-dominant B-cell recovery and declining autoantibodies indicate immune remodeling, not restored tolerance. No indirect efficacy ranking is justified. Prospective studies need standardized disease endpoints, treatment-free remission definitions, analyte-specific pharmacokinetics, paired blood–tissue pharmacodynamics, and long-term genomic, immune, and safety surveillance.
SN - 1664-3224
ER -