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162a Update on Kinoids as an Active Immunotherapy to Combat Pathogenic Cytokines in Viral, Cancer and Autoimmune Diseases: Safety, Immunogenicty

Zagury, Daniel1; Gougeon, Marie-Lise2; Boissier, Marie-Christophe3; Abitbol, Marc4; Lebuanec, Hélène2; Burny, Arsène5; Gallo, Robert C6

JAIDS Journal of Acquired Immune Deficiency Syndromes: April 2011 - Volume 56 - Issue - p 68
doi: 10.1097/01.qai.0000397349.30674.f6

1Neovacs 3/5 Impasse Reille Paris France; 2Institut Pasteur, Paris; 3Université Paris 13, Hôpital Avicenne AP-HP, Bobigny, France; 4Centre de Recherche Thérapeutique en Ophtalmologie, Université Paris-Descartes, Paris; 5ULB-IBMM, Gosselies, Belgium; and 6Institut of Human Virology, University of Maryland, Baltimore MD

Kinoids are a derivative of biologically non toxic but immunogenic cytokines prepared either by chemical inactivation of the cytokine (1rst generation) or by coupling the cytokine to a carrier protein such as KLH (2nd generation). Given that abnormal overproduction of cytokines are involved in the pathogenesis of severe chronic diseases, including AIDS (IFN α and IL 10), autoimmune diseases (TNF α and IFN α) and cancer (VEGF and TNF α), Kinoids have been experimentally assayed and are currently under clinical trials. In AIDS, inactivated IFN α has been efficiently used in a phase 2 EURIS trial (1). In Rheumatoid Arthritis TNF α-Kinoid immunotherapy proved to be safe and effective in transgenic hTNF α mice developing arthritis (2) and is currently under phase 1-2 trial in Crohn's disease and Rheumatoid Arthritis (NCT00808262). VEGF-Kinoid immunotherapy proved to be experimentally safe and effective in preventing the tumor development in a model of SCID or nude mice (3) and the neovessels sprouting in a murine model of choroidal neovascularization as it occurs in Age-related Macular Degeneration (AMD) and in choroidal melanoma.

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1. Gringeri A, et al. Active anti-interferon-alpha immunization: a European-Israeli, randomized, double-blind, placebo-controlled clinical trial in 242 HIV-1–infected patients (the EURIS study). J Acquir Immune Defic Syndr Hum Retrovirol. 1999;20:358-70.
2. Le Buanec H, et al. TNFalpha kinoid vaccination-induced neutralizing antibodies to TNFalpha protect mice from autologous TNFalpha-driven chronic and acute inflammation. Proc Natl Acad Sci U S A. 2006;103:19442-7.
3. Rad FH, et al. VEGF kinoid vaccine, a therapeutic approach against tumor angiogenesis and metastases. Proc Natl Acad Sci U S A. 2007;104:2837-42.
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