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

Abstract

ABSTRACTAnti-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.