CD45-ADC conditioning for Fanconi anemia patients undergoing allo-HSCT
Saha A, Palchaudhuri R, Lanieri L, et al. Alloengraftment Without Significant Toxicity or GVHD in CD45 Antibody-Drug Conjugate Conditioned Fanconi Anemia Mice. Blood. 2024; (doi: 10.1182/blood.2023023549).
Evidence suggests conditioning with CD45-targeted antibody-drug-conjugates (CD45-ADC) may benefit patients with Fanconi anemia (FA) who undergo allogeneic hematopoietic stem cell transplantation (allo-HSCT). The genetic DNA repair disorder typically presents with bone marrow failure, abnormal development, myelodysplasia, and a predisposition for leukemia and solid tumors; but toxicities and the potential for graft-versus-host disease (GVHD) associated with allo-HSCTcomplicate treatment. In three separate murine models of FA, a single dose of CD45-ADC conditioning before allo-HSCT promoted donor stem cell alloengraftment by opening marrow niches. Peripheral blood mean donor chimerism ranged from 60%-90% across the three models. None of the CD45-ADC conditioned mice developed clinical toxicity, and severe GVHD was significantly reduced in CD45-ADC recipients compared with mice that underwent lethal irradiation conditioning.