CD45: a niche marker for allotransplantation

In this issue of Blood, Saha et al(1) have identified a CD45-targeted antibodydrug conjugate (CD45 ADC) as a safe and highly effective conditioning agent for hematopoietic stem cell transplantation (HSCT) in a mouse model. Broad application of HSCT as curative treatment of blood disorders is limited by both donor incompatibility and the damage caused by current protocols using nonselective and genotoxic conditioning agents needed to make space for donor cells in the recipient hematopoietic stem cell (HSC) niche. Successful translation of this new CD45 ADC concept to the clinic has the potential to flatten the risk-benefit ratio in allotransplantation, turning the fantasy of a universal bone marrow donor into a reality and expanding transplantation applications from malignancy and inherited diseases of the blood to acquired diseases, including HIV/AIDS and autoimmunity. Possibly even solid organ allotransplantation might be included, because establishing a state of bone marrow chimerism has been known since the 1940s to establish a state of donor-specific solid organ allograft tolerance.(2) In sum, work in this area may augur a second and even broader transformation of medical practice by bone marrow transplantation.