Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity
| Autor: | Chunli Huang, Paul D. Lira, Love Victoria Alexandria, Oliphant Theodore Lawrence, Leslie L. Sharp, Sharon A. Sokolowski, Simon Bergqvist, Amy C. Shen, Rohner Allison Karlyn, Timothy Scott Fisher, Sangita M. Baxi, Regis Doyonnas, Cris Kamperschroer |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Agonist Cancer Research medicine.drug_class T-Lymphocytes medicine.medical_treatment T cell Immunology Biology Pharmacology Antibodies Monoclonal Humanized Lymphocyte Activation Monoclonal antibody Mice Immune system Cell Line Tumor medicine Animals Humans Immunology and Allergy Leukocyte proliferation Cell Proliferation CD137 NF-kappa B Antibodies Monoclonal Immunotherapy Xenograft Model Antitumor Assays Macaca fascicularis 4-1BB Ligand Cytokine medicine.anatomical_structure Oncology Immunoglobulin G Leukocytes Mononuclear Female |
| Zdroj: | Cancer Immunology, Immunotherapy. 61:1721-1733 |
| ISSN: | 1432-0851 0340-7004 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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