Antigen-specific regulatory cell therapy approaches in kidney transplantation

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.

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.

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.

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.