Abstract
Chimeric antigen receptor (CAR) T cells can achieve sustained clinical benefit in B cell malignancies and autoimmune diseases. Despite the many potential advantages over autologous products, allogeneic CAR T cells carry a higher risk of rejection, which may limit persistence and therapeutic efficacy. We report the design and evaluation of an optimized CD70 CAR that prevents rejection of allogeneic CAR T cells by targeting activated alloreactive lymphocytes. Co-expression of this CD70 CAR with a CD19 CAR resulted in sustained CAR T cell persistence in the presence of alloreactive lymphocytes and prolonged antitumor activity in a CD19 antigen escape model. In vivo, CD19/CD70 dual CAR T cells eliminated B cells and CD70+ T cells derived from patients with systemic lupus erythematosus in humanized mouse models, resulting in reduced immunoglobulin production. An allogeneic CD19/CD70 dual CAR T cell therapy may therefore broaden clinical applicability while enabling the use of less intensive lymphodepleting conditioning regimens prior to CAR T cell infusion.
Data availability
All raw and processed data supporting the findings of this study are provided herein and in the Source Data file. No additional datasets were generated. Source data are provided with this paper.
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Acknowledgements
We thank the vivarium staff for their expert support with animal studies and Yanqi Chang for the helpful suggestions and for providing support with AAV reagents.
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E.J.L. and C.S. designed the studies and interpreted the data. K.Z., Z.L., M.K.O., A.M., D.N., H.C., D.H., D.Q., and S.G. performed experiments. E.J.L., Z.J.R., and C.S. wrote the manuscript and are responsible for the integrity of the work as a whole.
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All authors are current or former employees of Allogene Therapeutics, Inc.
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Zhang, K., Li, Z., O’Dair, M.K. et al. Allogeneic CD19 CAR T cells armed with an anti-rejection CD70 CAR overcome antigen escape and evade alloimmune responses. Nat Commun (2026). https://doi.org/10.1038/s41467-026-71904-z
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DOI: https://doi.org/10.1038/s41467-026-71904-z
