Development of a humanized mice model for the study of humanized anti-IL7R antibodies in the treatment of acute lymphocytic leukemia

• Grant number: 24/01331-5
• Support Opportunities: Scholarships in Brazil - Master
• Start date: March 01, 2024
• End date: February 28, 2026
• Field of knowledge: Biological Sciences - Immunology - Applied Immunology
• Principal Investigator: Priscila Pini Zenatti Salles
• Grantee: Maysa de Souza Cavalcante
• 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
• Associated scholarship(s): 25/06682-3 - Enhancing Adaptive Immunity in THX Mice: Metabolite-Driven Strategies for Improved Antibody Responses, BE.EP.MS

Abstract

The use of immunocompetent murine models is a frequent and necessary practice in various biomedical research. However, critical genetic and immunological differences between the murine and human systems have hindered the development of in vivo studies that require a uniquely human immunological response. One way to overcome this difficulty is to generate humanized mice from immunosuppressed mice (SCID), with a mutation in the IL2R gene. These animals have immature B and T lymphocytes and a total block in the development of NK (Natural Killer) cells. Therefore, for this project, the objective is to develop and standardize the process of generating humanized mice by grafting human hematopoietic stem cells into immunodeficient animals. To validate the use of this model in preclinical tests, humanized animals will be transplanted with pediatric lymphocytic leukemia and the therapeutic effect of the murine anti-IL7R monoclonal antibody (mAb#64) on disease progression will be tested. This animal model will serve as a tool for future studies in oncology, autoimmune diseases, among others.