Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity

Cancer Immunol Immunother. 2012 Oct;61(10):1721-33. doi: 10.1007/s00262-012-1237-1. Epub 2012 Mar 11.

Abstract

4-1BB (CD137, TNFRSF9) is a costimulatory receptor expressed on several subsets of activated immune cells. Numerous studies of mouse and human T cells indicate that 4-1BB promotes cellular proliferation, survival, and cytokine production. 4-1BB agonist mAbs have demonstrated efficacy in prophylactic and therapeutic settings in both monotherapy and combination therapy tumor models and have established durable anti-tumor protective T-cell memory responses. PF-05082566 is a fully human IgG2 that binds to the extracellular domain of human 4-1BB with high affinity and specificity. In preclinical studies, this agonist antibody demonstrated its ability to activate NF-κB and induce downstream cytokine production, promote leukocyte proliferation, and inhibit tumor growth in a human PBMC xenograft tumor model. The mechanism of action and robust anti-tumor efficacy of PF-05082566 support its clinical development for the treatment of a broad spectrum of human malignancies.

MeSH terms

  • 4-1BB Ligand / agonists*
  • 4-1BB Ligand / immunology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Macaca fascicularis
  • Male
  • Mice
  • NF-kappa B / immunology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • Xenograft Model Antitumor Assays

Substances

  • 4-1BB Ligand
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Immunoglobulin G
  • NF-kappa B
  • utomilumab