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01.10.2012 | Original article

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

verfasst von: 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. Sharp

Erschienen in: Cancer Immunology, Immunotherapy | Ausgabe 10/2012

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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.

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Titel: Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity
verfasst von: 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. Sharp
Publikationsdatum: 01.10.2012
Verlag: Springer-Verlag
Erschienen in: Cancer Immunology, Immunotherapy / Ausgabe 10/2012
Print ISSN: 0340-7004
Elektronische ISSN: 1432-0851
DOI: https://doi.org/10.1007/s00262-012-1237-1

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Springer Medizin

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

Abstract

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