Characterization and functional validation of humanized anti-IL7Ra antibody for the treatment of Pediatric Leukemia

• Grant number: 23/11088-8
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: September 01, 2023
• End date: January 31, 2028
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Priscila Pini Zenatti Salles
• Grantee: Fernando Mesquita de Sousa de Lima
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil
• Associated research grant: 21/04137-7 - Monoclonal antibodies against pediatric Acute Lymphoblastic Leukemia, AP.JP

Abstract

The genetic association of IL7R with several diseases, especially leukemia, qualifies it as a potential target for the development of therapies in conditions of uncontrolled cell proliferation and survival. Approximately 10% of childhood ALL have an oncogenic mutation in IL7Ra. We obtained murine anti-IL7R antibodies that recognize both the wild form (WT) and the mutated form of IL7R±, which show therapeutic potential against ALL, both in vitro and in mouse PDX models. However, approximately 50 to 80% of patients receiving 100% murine antibody therapies develop a disease called HAMA (human anti-murine antibody antibodies) after a single dose. The process of humanization of antibodies reduces to 3% the murine portions in the sequence of the antibody and, consequently, becomes less immunogenic. Therefore, to enable a possible inclusion of these biodrugs in the treatment protocols of childhood leukemia and even autoimmune diseases, this project proposes to obtain the humanized version of the murine antibody (clone mAb#64) and validate it for therapeutic potential. (AU)