92R Monoclonal Antibody Inhibits Human CCR9+ Leukemia Cells Growth in NSG Mice Xenografts

• Main Authors: Beatriz Somovilla-Crespo, Maria Teresa Martín Monzón, Maria Vela, Isabel Corraliza-Gorjón, Silvia Santamaria, Jose A. Garcia-Sanz, Leonor Kremer
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2018-01-01
• Series: Frontiers in Immunology
• Subjects: cancer; therapeutic antibodies; combinations; oncology; chemokine receptors
• Online Access: http://journal.frontiersin.org/article/10.3389/fimmu.2018.00077/full

CCR9 is as an interesting target for the treatment of human CCR9+-T cell acute lymphoblastic leukemia, since its expression is limited to immature cells in the thymus, infiltrating leukocytes in the small intestine and a small fraction of mature circulating T lymphocytes. 92R, a new mouse mAb (IgG2a isotype), was raised using the A-isoform of hCCR9 as immunogen. Its initial characterization demonstrates that binds with high affinity to the CCR9 N-terminal domain, competing with the previously described 91R mAb for receptor binding. 92R inhibits human CCR9+ tumor growth in T and B-cell deficient Rag2−/− mice. In vitro assays suggested complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity as possible in vivo mechanisms of action. Unexpectedly, 92R strongly inhibited tumor growth also in a model with compromised NK and complement activities, suggesting that other mechanisms, including phagocytosis or apoptosis, might also be playing a role on 92R-mediated tumor elimination. Taken together, these data contribute to strengthen the hypothesis of the immune system’s opportunistic nature.