Periodic Reporting for period 1 - IL7RsignaTHER (Antibody-based IL-7R targeted therapies)
Okres sprawozdawczy: 2020-01-01 do 2021-12-31
Acute lymphoblastic leukemia (ALL), a highly aggressive hematological cancer, is the most frequent childhood malignancy and the second most common acute leukemia in adults. Despite remarkable improvements in treatment outcome of pediatric cases using conventional chemotherapy, with more than 80% of children with ALL being alive and disease-free at 5 years, a significant number of relapses still occur, whose prognosis is dismal. Moreover, 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 the need 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. In the current proposal we aimed to explore the dependence of T-cell ALL (T-ALL) cells on IL-7/IL-7R-mediated signaling and the broad expression of IL-7R on the surface of T-ALL cells to develop novel monoclonal antibody-based biopharmaceuticals to target the IL-7/IL-7R axis for treatment of T-ALL. We have developed and performed the initial characterization and selection of a set of high affinity antibodies that effectively bind IL-7R in the presence of IL-7 which we will further characterize for their anti-leukemia efficacy in models of the disease. A spin-out to explore our novel monoclonal antibody-based IL-7/IL-7R-mediated therapeutic strategy is expected to be officially created in order to facilitate subsequent steps toward clinical translation of our project’s outcomes.