A new step toward non-genotoxic conditioning prior to hematopoietic stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is the oldest, best developed, and most successful type of cell therapy in the field of regenerative medicine and the treatment of choice for a growing number of non-malignant and malignant diseases. Despite the broad curative potential of allogeneic and gene-modified autologous HSCT, these approaches are limited by the significant morbidity and mortality rates associated with the pretransplant conditioning regimen, which is needed to eradicate the patient's own HSCs, kill any residual malignant cells, and establish potent immunosuppression in allogeneic settings. Given the genotoxic effects of these conditioning regimens, significant effort has been devoted to identifying targets to reduce toxicity. Two of the most studied targets in the field of non-genotoxic conditioning regimens are the CD45 and c-Kit (also known as CD117) antigens. Comparatively speaking, CD45 has multiple advantages over c-Kit, including high expression on the HSC surface (at least 30 times more than c-Kit antigen), specificity for all hematopoietic cells including T cells, and few off-target effects. Moreover, the expression of CD45 on T-lymphocytes leads to the potent immunosuppression required for allogeneic HSCT.