LAUSR

Introduction: T cell immunotherapy using Chimeric AntigenReceptors (CA to generate tumor antigen-specific effector T cells has achieved excellent re in anti-leukemic clinical trials, and in a broader appraisal, promising immuno apeutic results. Amajor problem in solid organ transplantation is the presence in the re ient of donor specific antibodies, which preclude the success of the transp due to the associated high risk of antibody-mediated rejection. Methods: we hypothesize that a CAR (chimeric antigen receptor)-like m cule with a particular HLA molecule as the CAR extracellular domain wil gineer T cells to kill alloimmune B cells with anti-HLA antibodies as B completely eliminating alloantibodies in a specific manner. Results: first step was to create this chimeric receptor with the HLA-A2 tigen as the CAR-like extracellular domain: extracellular domains of HLA-A*02:01 molecule were amplified by PCR from cDNA of an A*02:01 itive donor. ACAR comprising the extracellular domains of HLA-A2 and 4-1 CD3ζ signalling domainwas constructed anddelivered by lentiviral transdu into human T cells. The cytotoxic capacity of these transduced T cells was assessed by culturing them with EBV-transformed B cells which produce anti-HLA alloantibodies. Conclusion: specific T cells directed to kill anti-HLA alloantibody produ B cells can be generated by means of the use of an HLA CAR-like rece This technology could open new ways of treatment and prevention of body-mediated rejection in solid organ transplantation.