Therapeutics: CD45

Mouse studies suggest an anti-CD45 mAb-based antibody-drug conjugate (ADC) could help condition patients for hematopoietic stem cell transplants (HSCTs). In a mouse model of HSCT, an ADC consisting of an anti-CD45 mAb linked to the ribosome-inactivating toxin saporin depleted host hematopoietic cells and enabled engraftment of donor cells with potency comparable to sublethal irradiation, and restored bone marrow cellularity faster and preserved bone marrow and thymic architecture with greater integrity than irradiation. In a mouse model of sickle cell anemia, ADC conditioning followed by HSCT transplant resulted in over 90% donor chimerism at four months post-transplantation and reduced disease phenotypes, including mutant hemoglobin in the blood, sickle-shaped red blood cells and splenomegaly. Next steps include testing the ADC in non-human primate models of HSCT (see "Killing HSCs Softly," page 17). ...