PMID: 9191886Jul 1, 1997Paper

A primatized MAb to human CD4 causes receptor modulation, without marked reduction in CD4+ T cells in chimpanzees: in vitro and in vivo characterization of a MAb (IDEC-CE9.1) to human CD4

Clinical Immunology and Immunopathology
D AndersonA Truneh

Abstract

A Primatized anti-CD4 monoclonal antibody (MAb), CE9.1, with V-domain from cynomolgus macaque (showing 92% homology with human consensus sequence V-domains), and a human IgG1 constant region, was characterized in vitro and in vivo in chimpanzees. This MAb binds human CD4 with Kd of 1.0 nM and was also able to bind to human IgG Fc receptors (Fc gamma R). However, despite being of the IgG1 subclass, CE9.1 did not bind to complement component C1q, nor did it mediate complement-dependent cytotoxicity. Examination of T cells from a number of species showed restricted reactivity for CE9.1, recognizing only human and chimpanzee CD4. In both human and chimpanzee MLRs, it had an IC50 of about 10.0 ng/mL. Therefore, a chimpanzee in vivo model was used to characterize CE9.1, CE9.1 caused transient decrease in the number of lymphocytes bearing the CD4 receptor starting at doses of 0.3 mg/kg in an in vivo dose ranging study in one chimpanzee. This effect was reversed within approximately 7 days. In a multiple high-dose study in which 10.0 mg/kg of CE9.1 was administered at intervals of 1-3 months, there was a dramatic loss of CD4 marker with a reciprocal increase in the number of CD3+ CD8- CD4- cells. The CD4 receptor was totally undetectab...Continue Reading

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Citations

Jul 5, 2003·Journal of Tongji Medical University = Tong Ji Yi Ke Da Xue Xue Bao·G ShenS Wang
Jun 10, 2011·Archives of Pharmacal Research·Jue-Hee Lee, Yongmoon Han
Aug 28, 2003·Current Opinion in Chemical Biology·Herman Waldmann
Sep 2, 2008·International Immunopharmacology·Jue-Hee LeeYongmoon Han
May 19, 2010·Expert Review of Clinical Immunology·Peter J BugelskiEsther Bouman-Thio
Jun 15, 1999·Toxicologic Pathology·K A GossettT S Sellers
Jul 16, 2014·World Journal of Hepatology·Marta Casal MouraGuilherme Macedo
Jul 5, 2005·World Journal of Gastroenterology : WJG·Bing YuGuan-Xin Shen
Feb 5, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M P ReddyA Truneh
Oct 24, 2000·Journal of Structural Biology·Y G KuznetsovA McPherson
Jan 24, 2006·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Samuel TroadecThierry Chardès

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