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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología terapia génica > DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista >

Multi-layered action mechanisms of CD137 (4-1BB)-targeted immunotherapies
Authors: Melero, I. (Ignacio)
Murillo, O. (Oihana)
Dubrot, J. (Juan)
Herbas-Stubbs, S. (Sandra)
Perez-Gracia, J.L. (José Luis)
Keywords: Antibodies, Monoclonal/therapeutic use
Antigens, CD137/metabolism
Immunotherapy/methods
Issue Date: 2008
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0165614708001375
ISSN: 1873-3735
Citation: Melero I, Murillo O, Dubrot J, Hervas-Stubbs S, Perez-Gracia JL. Multi-layered action mechanisms of CD137 (4-1BB)-targeted immunotherapies. Trends Pharmacol Sci 2008 Aug;29(8):383-390.
Abstract
CD137 (also known as 4-1BB) is a surface co-stimulatory glycoprotein originally described as present on activated T lymphocytes. Artificial stimulation of this molecule with monoclonal antibodies or other agonist moieties therapeutically augments the cellular immune response against tumors, regardless of the absence of CD137 on tumor cells. These pharmacological agents, when administered systemically, surpass the immune effects of the membrane-bound natural ligand (CD137 or 4-1BB ligand), the activity of which is confined to cell-to-cell interactions. Greater affinity and broader distribution of the CD137 pharmacological agonists cause much more intense receptor crosslinking and stronger intracellular signals than the natural ligand. Target engagement on a variety of immune cell types such as T, natural killer and dendritic cells and on tumor vessels could switch on multiple mechanisms of action. As an agonist, anti-CD137 monoclonal antibody has entered Phase II clinical trials; elucidation of the mechanisms behind the antitumor efficacy requires further research in mice and patients to understand and rationally combine these new treatments.
Permanent link: http://hdl.handle.net/10171/21769
Appears in Collections:DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología terapia génica - Artículos de revista

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