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bioRxiv · 10.1101/2025.09.10.674224

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

Petersen, M. I.·Lin, J.·Zhan, K.·Anwar, P.·Bockermann, R.·Anderson, C. C.
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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.

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Petersen, M. I., Lin, J., Zhan, K., Anwar, P., Bockermann, R., Anderson, C. C.. 2025-09-16. Imlifidase and EndoS enables semi-allogeneic bone marrow engraftment in sensitized mice under reduced intensity conditioning. https://doi.org/10.1101/2025.09.10.674224

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