Therapeutic Opportunities for Immunoreceptor-Engineered T Cell Therapy for Modulation of Alloimmunity [TRANSLATING IMMUNOLOGY]

Abstract

Achieving immunosuppression-free immune tolerance to an allograft is one of the central goals of transplantation. In this article, we review recent developments in the fields of T cell–based therapies and T cell engineering using chimeric Ag receptors and their potential for effective and targeted immune modulation of T and B cell activity in an effort to eliminate pre-existing alloantibodies (desensitization) and achieve long-term tolerance. Approaches that span preclinical to early clinical studies in transplantation will be reviewed, with specific emphasis on advances in T cell immunotherapy that have shown promise. Lastly, we conclude with a forward-looking discussion of how T cell–based therapies in other fields of medicine can be potentially applied to solid organ transplantation.

Footnotes

This work was supported by the Institute for Translational Medicine and Therapeutics at Penn (K.M.), Gift of Life Transplant Foundation (A.N. and V.G.B.), Burroughs Wellcome Fund (Grant 100000861 to V.G.B.), and The Colton Center for Autoimmunity at Penn (V.G.B.). V.G.B. received research funding from Cabaletta Bio.

Abbreviations used in this article:

BCMAB cell maturation Agβ2Mβ2-microglobulinCARchimeric Ag receptorDSAdonor specific AbLLPClong-lived plasma cellMHC-IMHC class ITregregulatory T cellReceived July 26, 2022.Accepted September 7, 2022.Copyright © 2022 by The American Association of Immunologists, Inc.

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