Hematopoietic stem cell transplants (HCT) can cure deadly blood cancers, including leukemias and lymphomas, but the powerful chemotherapy and radiation used to prepare patients for HCT cause serious short- long-term side effects, including organ damage, infertility, immune dysfunction, and secondary cancers. These risks are especially concerning for children due to their ongoing growth, pubertal development, and longer life expectancy, which allows more time for late complications to manifest.
Therefore, they are particularly vulnerable to dysfunctions in the endocrine system, puberty and growth, skeletal health, as well as cardiovascular and metabolic systems. Additionally, many patients, particularly those with prior treatments or organ damage, cannot safely receive a transplant.
To make HCT safer, we are testing a new approach using an antibody-drug conjugate (called ‘CD45-ADC’) that precisely targets blood-forming cells while sparing healthy tissues and organs. In our study, we will use a non-human primate model to determine if the CD45-ADC can replace traditional preparative agents, such as chemotherapy and radiation, leading to successful donor stem cell engraftment with fewer toxic effects. We will also examine how well the immune system recovers after transplant, focusing on the thymus. If successful, this strategy could be quickly translated to the clinic and may dramatically reduce transplant complications, making HCT an option for more patients and improving long-term health outcomes.
