期刊
BLOOD
卷 117, 期 8, 页码 2423-2432出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2010-08-301945
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资金
- National Institutes of Health [CA34233, CA33399, AI56363, AI057157]
- Leukemia & Lymphoma Society Specialized Center of Research (SCOR)
- Howard Hughes Medical Institute
- Foundation de France
- Association pour la Recherche sur le Cancer
Antibody-dependent cell-mediated cytotoxicity (ADCC), which is largely mediated by natural killer (NK) cells, is thought to play an important role in the efficacy of rituximab, an anti-CD20 monoclonal antibody (mAb) used to treat patients with B-cell lymphomas. CD137 is a costimulatory molecule expressed on a variety of immune cells after activation, including NK cells. In the present study, we show that an anti-CD137 agonistic mAb enhances the antilymphoma activity of rituximab by enhancing ADCC. Human NK cells up-regulate CD137 after encountering rituximab-coated tumor B cells, and subsequent stimulation of these NK cells with anti-CD137 mAb enhances rituximab-dependent cytotoxicity against the lymphoma cells. In a syngeneic murine lymphoma model and in a xenotransplanted human lymphoma model, sequential administration of anti-CD20 mAb followed by anti-CD137 mAb had potent antilymphoma activity in vivo. These results support a novel, sequential antibody approach against B-cell malignancies by targeting first the tumor and then the host immune system. (Blood. 2011;117(8):2423-2432)
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