title: Immunotherapy targeting 4-1BB and its ligand.
abstract: T-cell activation in the absence of costimulation is futile because T-cells deprived of costimulatory signals enter a state of unresponsiveness or anergy. The interaction of 4-1BB and 4-1BB ligand (4-1BBL) activates an important costimulatory pathway with diverse and important roles in immune regulation. Signals relayed through 4-1BB generate strong CD8(+) T-cell responses rather than CD4(+) T-cell responses; this action results in cytokine induction and promotes T-cell survival. In recent years, 4-1BB-mediated immune regulation has gained great significance because of the seemingly contradictory dual roles of agonistic anti-4-1BB in vivo disease models. To date, agonistic 4-1BB monoclonal antibody has shown therapeutic potential against a variety of tumors, CD4(+) T-cell-mediated autoimmune diseases, and chronic graft-versus-host disease. In addition, blockade of 4-1BB/4-1BBL interaction has produced therapeutic effects against coxsackievirus-induced myocardial inflammation, herpetic stromal keratitis, and graft rejection. We propose that the dual roles of agonistic anti-4-1BB--an enhanced effector function and a suppressor function--are mediated by a novel CD11c(+)CD8(+) T-cell population.
authors.affiliation: Department of Ophthalmology, LSU Eye Center, Louisiana State University Health Sciences Center School of Medicine, New Orleans, USA.
authors.forename: Dass S
authors.initials: DS
authors.lastname: Vinay
authors.forename: Byoung S
authors.initials: BS
authors.lastname: Kwon
mesh_terms: D053330:4-1BB Ligand; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D015703:Antigens, CD / Q000276:immunology*; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D003384:Coxsackievirus Infections / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D006801:Humans; D007167:Immunotherapy; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000473:pathology; D000079424:Tumor Necrosis Factor Inhibitors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D048069:Tumor Necrosis Factors / Q000276:immunology*
chemical_list: D053330:4-1BB Ligand; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D017475:Receptors, Nerve Growth Factor; D018124:Receptors, Tumor Necrosis Factor; C505714:TNFRSF9 protein, human; C505974:TNFSF9 protein, human; D000079424:Tumor Necrosis Factor Inhibitors; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D048069:Tumor Necrosis Factors