CAR T-cell therapy- Paving the way for sensitized kidney transplant patients.

Jarmi, T.; Luo, Y.; Attieh, R. M.; Qie, Y.; Gadd, M. E.; Hundal, T.; Mao, S.; Murthy, H. S.; Taner, B. C.; Kharfan-Dabaja, M.; Qin, H.

doi:10.1101/2023.08.24.554644

bioRxiv · 10.1101/2023.08.24.554644

CAR T-cell therapy- Paving the way for sensitized kidney transplant patients.

Jarmi, T.·Luo, Y.·Attieh, R. M.·Qie, Y.·Gadd, M. E.·Hundal, T.·Mao, S.·Murthy, H. S.·Taner, B. C.·Kharfan-Dabaja, M.·Qin, H.

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Abstract

Anti-HLA donor specific antibodies have been extensively documented for their critical role in kidney transplant rejection and resulting adverse outcomes. Several approaches have been employed to desensitize these patients; however, none of these explored therapeutic approaches has exhibited enduring clinical benefits. In this study, we explore a novel strategy of utilizing chimeric antigen receptor T cells (CAR T-cells) to target B cells in sensitized kidney transplant recipients. Specifically, we investigate the potential of our innovative MC10029 CAR T-cells, which are designed to recognize the B cell activating factor receptor (BAFF-R). BAFF-R is predominantly expressed on mature B cells and plays a crucial role in their survival, as well as in the promotion of autoreactive B cell. Our data revealed that sensitized patients B cells exhibited high levels of BAFF-R expression. We have successfully generated patient-derived MC10029 CAR T-cells from 6 sensitized patients. All these patient-derived MC10029 CAR T-cells consistently exhibited antigen-specific cytotoxicity against autologous B cells, accompanied by the release of cytotoxic granules. We have recently obtained FDA approval of an Investigational New Drug application for MC10029 CAR T-cell therapy in B-cell hematological diseases. This significant milestone paves the way for the pioneering launch of a human clinical trial, marking the first-ever application of CAR T-cell therapy in sensitized patients waiting for life-saving organ transplants.

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Jarmi, T., Luo, Y., Attieh, R. M., Qie, Y., Gadd, M. E., Hundal, T., Mao, S., Murthy, H. S., Taner, B. C., Kharfan-Dabaja, M., Qin, H.. 2023-08-26. CAR T-cell therapy- Paving the way for sensitized kidney transplant patients.. https://doi.org/10.1101/2023.08.24.554644

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