CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Blood Année : 2011

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

Holbrook E. Kohrt
  • Fonction : Auteur
Roch Houot
Matthew J. Goldstein
  • Fonction : Auteur
Kipp Weiskopf
  • Fonction : Auteur
Ash A. Alizadeh
  • Fonction : Auteur
Josh Brody
  • Fonction : Auteur
Antonia Müller
  • Fonction : Auteur
Russell Pachynski
  • Fonction : Auteur
Debra Czerwinski
  • Fonction : Auteur
Steven Coutre
  • Fonction : Auteur
Mark P. Chao
  • Fonction : Auteur
Thomas F. Tedder
  • Fonction : Auteur
Ronald Levy
  • Fonction : Auteur

Résumé

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.

Domaines

Cancer

Dates et versions

hal-00743985 , version 1 (22-10-2012)

Identifiants

Citer

Holbrook E. Kohrt, Roch Houot, Matthew J. Goldstein, Kipp Weiskopf, Ash A. Alizadeh, et al.. CD137 stimulation enhances the antilymphoma activity of anti-CD20 antibodies.. Blood, 2011, 117 (8), pp.2423-32. ⟨10.1182/blood-2010-08-301945⟩. ⟨hal-00743985⟩
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