Antibody-based IL-7R targeted therapies

ended

Acute lymphoblastic leukemia (ALL), a highly aggressive hematological cancer, is the most frequent childhood malignancy and the second most common acute leukemia in adults. The use of risk-adjusted multi-agent intensive chemotherapy has led to a remarkable improvement in treatment outcome of pediatric cases, with more than 80% of children with ALL being alive and disease-free at 5 years. However, a significant number of relapses still occur, whose prognosis is dismal, and the intensive regimens used are often associated with long-term, severe complications. In adults, the scenario is considerably worse: only 30–40% of the cases achieve long-term remission. Therefore, there is an obvious unmet need, and a major challenge, to develop novel, more efficient therapeutic strategies that specifically target the leukemic cells, minimize the detrimental side effects associated with conventional therapies and improve overall treatment outcome. Based on exciting and robust preliminary data from our ERC Consolidator Grant IL7sigNETure (CoG-648455), we now propose to explore the dependence of ALL cells on IL-7/IL-7R-mediated signaling and the broad expression of IL-7R on the surface of ALL cells to develop and commercialize novel monoclonal antibody-based biopharmaceuticals that we will generate targeting the IL-7/IL-7R axis for treatment of this malignancy. Our innovative therapeutic strategies have significant market potential that extends beyond ALL. Other possible indications include other lymphoid malignancies (Hodgkin's lymphoma, peripheral T-cell lymphoma, chronic lymphocytic leukemia), solid cancers with ectopic expression of IL-7R (including melanoma, breast, lung, bladder and colorectal cancer, or glioblastoma), and autoimmune and chronic inflammatory diseases (diabetes, multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease) in which the IL-7/IL-7R axis plays a pathological role.