4.7 Article Retracted Publication

被撤回的出版物: CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies (Retracted article. See vol. 134, pg. 658, 2019)

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

  1. National Institutes of Health [CA34233, CA33399, AI56363, AI057157]
  2. Leukemia & Lymphoma Society Specialized Center of Research (SCOR)
  3. Howard Hughes Medical Institute
  4. Foundation de France
  5. Association pour la Recherche sur le Cancer

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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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