Antigen-specific regulatory cell therapy approaches in kidney transplantation
- 1Renal Division, Department of Medicine, UMass Chan Medical School
Abstract
Background: Antigen-specific regulatory T-cell therapies seek to control donor-reactive immunity while preserving broader immune protection. The available platforms differ substantially in cellular composition, mode of antigen recognition, manufacturing requirements, and maturity of clinical evidence.
Scope: This narrative Mini Review compares donor-cell expansion, costimulation-blockade products, peptide-based targeting of indirect allorecognition, CAR- and TCR-engineered Tregs, and Tr1-enriched products. Evidence is distinguished as ex vivo or mechanistic, preclinical in vivo , human non-kidney, kidney feasibility and safety, or suggestive of clinical activity.
Key insights: No platform is likely to suit every transplant setting. Donor-cell approaches provide broad antigenic coverage but require individualized donor material. Peptide and receptor-defined approaches offer precision and donor-independent manufacture but are constrained by antigen processing, HLA restriction, or incomplete coverage. Early CAR-Treg studies provide preliminary safety and proof-of-mechanism observations, not evidence of operational tolerance. Culture conditions, accompanying immunosuppression, and product-specific safety risks must be considered together.
Conclusions: Progress will require consistent nomenclature, mechanism-linked potency assays, quantitative reporting of clinical studies, and operational measures of persistence, regulatory stability, donor-specific function, graft engagement, and clinical durability. The near-term goal is safe and sustained immunosuppression minimization. Operational tolerance must be demonstrated rather than inferred.
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BibTeX
@article{tripathi2026antigenspecific,
title = {{Antigen-specific regulatory cell therapy approaches in kidney transplantation}},
author = {Sudipta Tripathi and Anil Chandraker},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1956545},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1956545/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Antigen-specific regulatory cell therapy approaches in kidney transplantation
AU - Sudipta Tripathi
AU - Anil Chandraker
PY - 2026
DA - 2026/10/21
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1956545
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1956545/full
AB - Background: Antigen-specific regulatory T-cell therapies seek to control donor-reactive immunity while preserving broader immune protection. The available platforms differ substantially in cellular composition, mode of antigen recognition, manufacturing requirements, and maturity of clinical evidence. Scope: This narrative Mini Review compares donor-cell expansion, costimulation-blockade products, peptide-based targeting of indirect allorecognition, CAR- and TCR-engineered Tregs, and Tr1-enriched products. Evidence is distinguished as ex vivo or mechanistic, preclinical in vivo , human non-kidney, kidney feasibility and safety, or suggestive of clinical activity. Key insights: No platform is likely to suit every transplant setting. Donor-cell approaches provide broad antigenic coverage but require individualized donor material. Peptide and receptor-defined approaches offer precision and donor-independent manufacture but are constrained by antigen processing, HLA restriction, or incomplete coverage. Early CAR-Treg studies provide preliminary safety and proof-of-mechanism observations, not evidence of operational tolerance. Culture conditions, accompanying immunosuppression, and product-specific safety risks must be considered together. Conclusions: Progress will require consistent nomenclature, mechanism-linked potency assays, quantitative reporting of clinical studies, and operational measures of persistence, regulatory stability, donor-specific function, graft engagement, and clinical durability. The near-term goal is safe and sustained immunosuppression minimization. Operational tolerance must be demonstrated rather than inferred.
SN - 1664-3224
ER -