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Chimeric anti-hIL7R antibodies: production and validation of your therapeutic potential in the treatment of Acute Lymphoid Leukemia

Grant number: 20/07706-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2020
Effective date (End): October 31, 2021
Field of knowledge:Biological Sciences - Immunology - Immunogenetics
Principal Investigator:Priscila Pini Zenatti
Grantee:Rhaissa Godoi
Home Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Leukemia is a cancer of hematopoietic cells, being characterized by uncontrolled and abnormal proliferation of leukocytes, impairing the production of other blood cells in the bone marrow. Acute Lymphoid Leukemia (B or T cell ALL) is the most common malignancy in children and, although diagnosis and treatment guarantee the child's survival, there are still high levels of relapse. IL-7 signaling is crucial for the development and survival of T lymphocytes, and its performance depends on the binding to its transmembrane receptor IL-7R. It is already known that the constitutive activation of its signaling pathways contributes to the progression of leukemia. Our research group demonstrated that 10% of patients with T-ALL have a mutation in the IL7R alpha chain, classifying it as an oncogene, a target of interest for immunotherapy. Antibodies are immunoglobulins capable of recognizing and binding specifically to antigens, and are a therapeutic target for cancer, as they contribute significantly to the treatment of malignancies. Its main mechanisms of action result in the death of the target cell recognized by the antibody, and may involve molecules of the complement system (CDC) or be mediated by effector cells (ADCC). Therefore, our research group produced a panel of therapeutic anti-hIL7Ra monoclonal antibodies and has already validated their potential to block the progression of leukemia in an animal model. This project aims to transform 3 murine anti-hIL7Ra antibodies, previously validated, into their corresponding chimeric forms. Only then, these biopharmaceuticals can be tested in humanized models and advance to the clinical stage in humans. The importance of this work is the possibility of obtaining therapeutic antibodies that can be incorporated into the treatment protocols of patients or even replace part of the chemotherapy currently used in the treatment of childhood ALL.