Cancer Immunology, Immunotherapy

, Volume 61, Issue 10, pp 1721–1733 | Cite as

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

  • Timothy S. Fisher
  • Cris Kamperschroer
  • Theodore Oliphant
  • Victoria A. Love
  • Paul D. Lira
  • Regis Doyonnas
  • Simon Bergqvist
  • Sangita M. Baxi
  • Allison Rohner
  • Amy C. Shen
  • Chunli Huang
  • Sharon A. Sokolowski
  • Leslie L. SharpEmail author
Original article


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.


CD137 TNFRSF9 Agonist monoclonal antibody Immunotherapy T cell Cancer 



We thank Pfizer La Jolla Comparative Medicine for animal support; Jerry Casperson, James Christensen and Steve Bender for project support; Bart Jessen, Robert Arch, Tim Paradis, Craig Davis, Karin Jooss and Mike Primiano for discussion of the manuscript.

Conflicts of interest

All authors are current or former employees of Pfizer Inc.

Supplementary material

262_2012_1237_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2005 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Timothy S. Fisher
    • 1
  • Cris Kamperschroer
    • 2
  • Theodore Oliphant
    • 5
  • Victoria A. Love
    • 1
  • Paul D. Lira
    • 1
  • Regis Doyonnas
    • 4
  • Simon Bergqvist
    • 1
  • Sangita M. Baxi
    • 1
  • Allison Rohner
    • 1
  • Amy C. Shen
    • 3
  • Chunli Huang
    • 3
  • Sharon A. Sokolowski
    • 3
  • Leslie L. Sharp
    • 1
    Email author
  1. 1.Oncology Research UnitPfizer Inc.San DiegoUSA
  2. 2.Immunotoxicology Center of Emphasis, Drug Safety Research and DevelopmentPfizer Inc.GrotonUSA
  3. 3.Biomarkers Flow Cytometry Core Facility, Drug Safety Research and DevelopmentPfizer Inc.GrotonUSA
  4. 4.Genetically Engineered Models Center of EmphasisPfizer Inc.GrotonUSA
  5. 5.Protein Therapeutics Center of EmphasisPfizer Inc.ChesterfieldUSA

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