title: Targeting of 4-1BB by monoclonal antibody PF-05082566 enhances T-cell function and promotes anti-tumor activity.
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.
authors.affiliation: Oncology Research Unit, Pfizer Inc., 10724 Science Center Drive, San Diego, CA 92121, USA.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Fisher
authors.forename: Cris
authors.initials: C
authors.lastname: Kamperschroer
authors.forename: Theodore
authors.initials: T
authors.lastname: Oliphant
authors.forename: Victoria A
authors.initials: VA
authors.lastname: Love
authors.forename: Paul D
authors.initials: PD
authors.lastname: Lira
authors.forename: Regis
authors.initials: R
authors.lastname: Doyonnas
authors.forename: Simon
authors.initials: S
authors.lastname: Bergqvist
authors.forename: Sangita M
authors.initials: SM
authors.lastname: Baxi
authors.forename: Allison
authors.initials: A
authors.lastname: Rohner
authors.forename: Amy C
authors.initials: AC
authors.lastname: Shen
authors.forename: Chunli
authors.initials: C
authors.lastname: Huang
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Sokolowski
authors.forename: Leslie L
authors.initials: LL
authors.lastname: Sharp
mesh_terms: D053330:4-1BB Ligand / Q000819:agonists* / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D016328:NF-kappa B; C577122:utomilumab