Adjuvant use of IL7 for stimulation of lymphopoiesis during chemotherapy in a murine model of Acute Lymphoblastic Leukemia

• Grant number: 24/22071-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2025
• End date: February 28, 2027
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: José Andrés Yunes
• Grantee: Victoria Albeck
• Host Institution: Centro Infantil de Investigações Hematológicas Dr Domingos A Boldrini (CIB). Campinas , SP, Brazil

Abstract

Acute lymphoblastic leukemia (ALL) is the most common cancer in children and adolescents, accounting for 25% of pediatric cancer cases. ALL treatment involves the combined use of various chemotherapeutic agents and lasts approximately two years. The amount of residual leukemic cells in the bone marrow of patients after one and three months of treatment is used to identify poor responders, who are subsequently treated more intensively.In addition to the presence of residual disease, some studies, including data from our group, show that the quality of bone marrow regeneration at the end of the first month of treatment is also associated with therapeutic response. Patients with greater immunoglobulin gene diversity exhibit better clinical outcomes than those whose bone marrow regeneration after chemotherapy fails to generate a high diversity of lymphocytes.Given that interleukin 7 (IL7) is the main cytokine involved in lymphopoiesis, this project aims to investigate, in an animal model of ALL, whether IL7 can stimulate lymphopoiesis and improve the survival of the animals. Initially, this hypothesis will be tested through in vitro experiments evaluating the competition between normal B-cell precursors from mice and primary murine ALL cells under IL7 stimulation. If it is confirmed that healthy B-cell precursors respond better than ALL cells, animal experiments will be initiated.Immunocompetent mice will be transplanted with murine ALL cells, and during or after chemotherapy similar to induction therapy in humans, one group will be treated with IL7 and compared to a control group. The survival of the animals and the diversity of B lymphocytes will be assessed.Additionally, a recombinant IL7 fused to Fc, which has an extended half-life, will be produced and evaluated in parallel. It is expected that IL7 will preferentially stimulate healthy B-cell precursors in the bone marrow, outcompeting ALL cells and prolonging animal survival.