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Pharmacological intervention on the immune system to achieve more intense lymphocyte responses has potential application in tumour immunology and in the treatment of chronic viral diseases. Immunostimulating monoclonal antibodies are defined as a new family of drugs that augment cellular immune responses. They interact as artificial ligands with functional proteins of the immune system, either activating or inhibiting their functions. There are humanized monoclonal antibodies directed to the inhibitory receptor CD152 (CTLA-4) that are being tested in clinical trials with evidence of antitumoural activity. As a drawback, anti-CTLA-4 monoclonal antibodies induce severe autoimmunity reactions in a fraction of the patients. Anti-CD137 monoclonal antibodies have the ability to induce potent immune responses mainly mediated by cytotoxic lymphocytes with the result of frequent complete tumour eradications in mice. Comparative studies in experimental models indicate that the antitumour activity of anti-CD137 monoclonal antibodies is superior to that of anti-CD152. CD137 (4-1BB) is a leukocyte differentiation antigen selectively expressed on the surface of activated T and NK lymphocytes, as well as on dendritic cells. Monoclonal antibodies acting as artificial stimulatory ligands of this receptor (anti-CD137 agonist antibodies) enhance cellular antitumoural and antiviral immunity in a variety of mouse models. Paradoxically, anti-CD137 monoclonal antibodies are therapeutic or preventive in the course of model autoimmune diseases in mice. In light of these experimental results, a number of research groups have humanized antibodies against human CD137 and early clinical trials are about to start.

Original publication

DOI

10.4321/s1137-66272006000100007

Type

Journal article

Journal

Anales del sistema sanitario de Navarra

Publication Date

01/2006

Volume

29

Pages

77 - 96

Addresses

Area de Terapia Génica y Hepatología, Centro de Investigación Médica Aplicada, Pamplona.

Keywords

Tumor Cells, Cultured, Animals, Mice, Transgenic, Humans, Mice, Virus Diseases, Neoplasms, Neoplasms, Experimental, Chronic Disease, Receptors, Tumor Necrosis Factor, Receptors, Nerve Growth Factor, Antineoplastic Agents, Antigens, Differentiation, Antigens, CD, Cancer Vaccines, Viral Vaccines, Antibodies, Monoclonal, Cytokines, Immunotherapy, Bone Marrow Transplantation, Transplantation, Homologous, Autoimmunity, Clinical Trials as Topic, Clinical Trials, Phase II as Topic, Clinical Trials, Phase III as Topic, CTLA-4 Antigen, Tumor Necrosis Factor Receptor Superfamily, Member 9