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CAR-Tregs as a Strategy for Inducing Graft Tolerance

  • Immunology (R Fairchild, Section Editor)
  • Published:
Current Transplantation Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

The adoptive transfer of alloantigen-specific regulatory T cells (Tregs) following organ transplantation is an emerging treatment paradigm that may induce tolerance and reduce the risk for graft rejection. In particular, redirecting Treg specificity via expression of synthetic chimeric antigen receptors (CARs) has demonstrated therapeutic promise in several preclinical studies. In this review, we highlight recent progress and remaining barriers to the clinical translation of CAR-Treg therapies.

Recent Findings

CAR Tregs targeting human leukocyte antigen (HLA)-A2 showed antigen-specific in vitro activation and superior in vivo protective function relative to polyclonal Tregs. Adoptively transferred anti-HLA-A2 CAR Tregs prolonged the survival of HLA-A2-positive grafts in humanized mouse models.

Summary

Donor HLA molecules are attractive candidate antigens to target with CAR Tregs in transplantation due to mismatched HLA only expressed on the transplanted organ. The feasibility of this approach has been demonstrated by several independent groups in recent years. However, substantial challenges in CAR design and preclinical modeling must be more extensively addressed prior to clinical application.

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Authors and Affiliations

  1. Department of Surgery, Division of Transplantation, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA, 94143, USA

    Johanna C. Wagner & Qizhi Tang

  2. Department of General, Visceral, Transplantation, Vascular and Pediatric Surgery, University Hospital Würzburg, Oberdürrbacherstr. 6, 97080, Würzburg, Germany

    Johanna C. Wagner

  3. UCSF Diabetes Center, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA, 94143, USA

    Qizhi Tang

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Wagner, J.C., Tang, Q. CAR-Tregs as a Strategy for Inducing Graft Tolerance. Curr Transpl Rep 7, 205–214 (2020). https://doi.org/10.1007/s40472-020-00285-z

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