Imlifidase and EndoS enables semi-allogeneic bone marrow engraftment in sensitized mice under reduced intensity conditioning

Abstract Patients in need of a hematopoietic stem cell transplant frequently have pre-existing donor-specific antibodies (DSA) which can impair engraftment. These patients often require intensified conditioning regimens, even in the setting of partially matched (semi-allogeneic) donors. Reducing the toxicity of conditioning and desensitization protocols is therefore a major goal. We previously showed that enzymatic desensitization of donor-specific IgG using imlifidase and EndoS improved murine bone marrow engraftment in donor sensitized, autoimmune-prone recipient mice. Conditioning included a 6 Gy total body irradiation, cyclophosphamide, bortezomib, and T cell depletion. In non-autoimmune prone semi-allogeneic recipients sensitized to the donor, we demonstrate that desensitisation with imlifidase and EndoS permits long-term donor bone marrow engraftment and induces tolerance to subsequent allogeneic skin grafts under a 3 Gy irradiation protocol. Enzymatic inactivation of DSA facilitates donor hematopoietic stem cell engraftment in allo-sensitized semi-allogeneic recipients in a reduced intensity conditioning protocol. Competing Interest Statement Robert Bockermann is employed by Hansa Biopharma and is a holder of shares or share warrants in Hansa Biopharma AB. Abbreviations - BMC - bone marrow cells - BMT - bone marrow transplantation - CyBor - bortezomib and cyclophosphamide - DSA - donor specific antibodies - EndoS - endoglycosidase of Streptococcus pyogenes - GVHD - graft-versus-host disease - IdeS - IgG degrading enzyme of Streptococcus pyogenes - IVIG - intravenous immune globulins - TBI - total body irradiation - HSC - hematopoietic stem cell