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HIV patients and GcMAF

Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)”

Serum Gc protein (known as vitamin D3-binding protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of HIV-infected patients was lost or reduced because Gc protein is deglycosylated by -N-acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression.Since Nagalase is the intrinsic component of the envelope protein gp120, serum Nagalase activity is the sum of enzyme activities carried by both HIV virions and envelope proteins. These Nagalase carriers were already complexed with anti-HIV immunoglobulin G (IgG) but retained Nagalase activity that is required for infectivity.

Stepwise treatment of purified Gc protein with immobilized -galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effects in humans. Macrophages activated by administration of 100 ng GcMAF develop a large amount of Fc-receptors as well as an enormous variation of receptors that recognize IgG-bound and unbound HIV virions.

Since latently HIV-infected cells are unstable and constantly release HIV virions, the activated macrophages rapidly intercept the released HIV virions to prevent reinfection resulting in exhaustion of infected cells.

After less than 18 weekly administrations of 100 ng GcMAF for nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV-infection, which was also confirmed by no infectious center formation by provirus inducing agent-treated patient PBMCs. No recurrence occurred and their healthy CD + cell counts were maintained for 7 years. J. Med. Virol. 81:16-26, 2009.

 

© 2008 Wiley-Liss, Inc.

Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF)
Nobuto Yamamoto  , Naofumi Ushijima , Yoshihiko Koga
1Division of Molecular Immunology and Immunotherapy, Socrates Institute for Therapeutic Immunology, Philadelphia, Pennsylvania
2Nakagawa Hospital, Fukuoka City, Japan
email: Nobuto Yamamoto ()

*Correspondence to Nobuto Yamamoto, Division of Molecular Immunology and Immunotherapy, Socrates Institute for Therapeutic Immunology, 1040 66th Ave., Philadelphia, PA 19126-3305.

Funded by:
US Public Health Service (partial support); Grant Number: AI-32140
Elsa U. Pardee Foundation (to N.Y.)

Keywords:

macrophages • macrophage activation • eradication of HIV • immunosuppression

 

Accepted: 18 September 2008

10.1002/jmv.21376  

Source: http://www3.interscience.wiley.com/journal/121531612/abstract

PDF http://www3.interscience.wiley.com/cgi-bin/fulltext/121531612/PDFSTART

 

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