AUTHOR=Muller Yannick D. , Ferreira Leonardo M. R. , Ronin Emilie , Ho Patrick , Nguyen Vinh , Faleo Gaetano , Zhou Yu , Lee Karim , Leung Kevin K. , Skartsis Nikolaos , Kaul Anupurna M. , Mulder Arend , Claas Frans H. J. , Wells James A. , Bluestone Jeffrey A. , Tang Qizhi TITLE=Precision Engineering of an Anti-HLA-A2 Chimeric Antigen Receptor in Regulatory T Cells for Transplant Immune Tolerance JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.686439 DOI=10.3389/fimmu.2021.686439 ISSN=1664-3224 ABSTRACT=
Infusion of regulatory T cells (Tregs) engineered with a chimeric antigen receptor (CAR) targeting donor-derived human leukocyte antigen (HLA) is a promising strategy to promote transplant tolerance. Here, we describe an anti-HLA-A2 CAR (A2-CAR) generated by grafting the complementarity-determining regions (CDRs) of a human monoclonal anti-HLA-A2 antibody into the framework regions of the Herceptin 4D5 single-chain variable fragment and fusing it with a CD28-ΞΆ signaling domain. The CDR-grafted A2-CAR maintained the specificity of the original antibody. We then generated HLA-A2 mono-specific human CAR Tregs either by deleting the endogenous T-cell receptor (TCR)