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Blood. 2011 Feb 24;117(8):2423-32. doi: 10.1182/blood-2010-08-301945. Epub 2010 Dec 30.

CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies.

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  • 1Department of Medicine, Division of Oncology, Stanford University Medical Center, Stanford, CA 94305, USA.

Abstract

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.

PMID:
21193697
[PubMed - indexed for MEDLINE]
PMCID:
PMC3062409
Free PMC Article
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