Optimization and preclinical testing of PR004384-anti-CD117xCD3-BiTE
In this public private partnership between Erasmus MC, Harbour Biomed and the biomedical primate center will optimize and preclinical test a novel reagent for safe bone marrow conditioning prior to hematopoietic stem cell transplantation.
Hematopoietic stem cell transplantation is a life-saving procedure for patients with benign and malignant hematological disorders. Its use, however, is hampered by two major hurdles: 1. Transplant conditioning-related toxicity, resulting in significant morbidity and mortality. This also limits the application of allotransplantation in the majority of patients that are not clinically fit enough. 2. Relapse of disease caused by surviving leukemia-initiating stem cells (LISCs) after pre-transplant chemotherapy. Thus, bone marrow (BM)-conditioning protocols prior to allotransplantation need improvement to prevent toxicities and relapse.
A successful anti-CD117 reagent would allow Harbour Biomed to expand in the area of AML cure, with more than 119.000 cases per year globally, of which more than 40.000 in Europe and 20.000 cases in USA. Although the group of immune-deficiencies, hemoglobinopathies and bone marrow failure patients is small, the impact of a low toxicity bone marrow conditioning treatment will be significant due to the expected increase of quality of life and strongly reduced risk of heart-failure, infertility and cancer. Our innovation triggers the patient’s own immune system to deplete diseased cells and rapidly prepares the patient for hematopoietic stem cell transplantation. We will first optimize our novel bone marrow conditioning and transplantation protocol and test unexpected toxicities in pre-clinical studies. In addition, we will optimize the reagent for large-scale production at clinical quality.
The expected pre-clinical data on toxicities of the treatment will ultimately allow for the initiation of phase-I clinical trials in which our innovative reagent will be tested as a novel bone marrow conditioning regimen in adult and childhood patients with hematological disorders at Erasmus MC and other (inter)-national institutes.
