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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kohrt, HE; Houot, R; Goldstein, MJ; Weiskopf, K; Alizadeh, AA; Brody, J; Müller, A; Pachynski, R; Czerwinski, D; Coutre, S; Chao, MP; Chen, L; Tedder, TF; Levy, R

Published Date

  • February 2011

Published In

Volume / Issue

  • 117 / 8

Start / End Page

  • 2423 - 2432

PubMed ID

  • 21193697

Pubmed Central ID

  • 21193697

Electronic International Standard Serial Number (EISSN)

  • 1528-0020

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-08-301945

Language

  • eng