Targeting IL7R with a monoclonal antibody for treating pediatric malignancy

Authors

• GOL Rodrigues
• JH Hixon
• W Li
• T Gower
• U Saini
• A Varadhachary
• S Durum

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer, classified into T-ALL and B-ALL based on the characteristics of immature lymphocytes. Currently, there are at least 23 recognized ALL subtypes with varying responses to chemotherapeutic and targeted regimens. While chemotherapy achieves 5-year overall survival rates of up to 90%, it is highly toxic in children, causing severe side effects, some lifelong, and relapsed cases have a poor prognosis. The IL-7 pathway is essential for normal T cell development and has roles in early B cell development. The IL7R (CD127) is expressed by the majority of both T-ALL and B-ALL, and oncogenic mutations in the IL7R pathway have been reported in both T-ALL and B-ALL.
Our lab developed new anti-IL-7Rα monoclonal antibodies (MAbs). Following the model of anti-CD20 MAbs used clinically in lymphoma, these anti-CD127 MAbs were chimerized with human IgG1/κ constant regions and induced in vitro killing of T-ALL cells mediated by both NK cells (ADCC) and macrophages (ADCP). T-ALL patient-derived xenografts (PDXs) treated with anti-IL-7Rα MAbs showed therapeutic benefits. Anti-CD127/Mab proved effective as a single agent against T-ALL PDXs, reducing leukemic burden in blood and bone marrow, and improving survival.
Here, we demonstrate that anti-CD127/Mab can also treat B-ALL PDXs, including a dexamethasone-resistant B-ALL, suggesting potential benefits for patients resistant to dexamethasone, a commonly used corticosteroid in leukemia treatment. Our findings indicate that anti-CD127/Mab can treat B-ALL and potentially other leukemias frequently expressing IL-7R, offering a promising therapeutic option for these conditions.

Scientific Focus Area: Immunology

This page was last updated on Tuesday, August 6, 2024