Sa.125 Therapeutic Efficacy of the Most Potent Macrophage Activating Factor (GcMAF) for Prostate and Breast Cancers Nobuto Yamamoto, Director, Socrates Institute for Therapeutic Immunology, Philadelphia, PA, Masumi Ueda, Chief, Microbiology Department, Socrates Institute for Therapeutic Immunology, Philadelphia, PA, Charles Benson, Head, Infectious Diseases, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA Inflammation-primed macrophage activation is the principal macrophage activation process that requires serum vitamin D-binding protein (known as Gc protein) and participation of B and T lymphocytes. A trisaccharide composed of N-acetylgalactosamine with dibranched galactose and sialic acid termini at 420 threonine residue of Gc protein is hydrolyzed by the β-galactosidase (Bgl) of inflammation-primed B cells and the Neu-1 sialidase of T cells to yield the macrophage activating factor (MAF). Thus, Gc protein is the precursor for the principal MAF. However, the MAF precursor activity of serum Gc protein of cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Serum Nagalase activity is proportional to tumor burden and serves as a prognostic index. Stepwise treatment of highly purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage activating factor (GcMAF) that produces no side effect in humans. When human macrophages were treated in vitro with GcMAF (100 pg/ml) for 3 h, the macrophages developed enormous variation of receptors that recognize a variety of cellular abnormalities, i.e., tumor associated antigens, in cancerous cell surface. Thus, the activated macrophages were highly tumoricidal to a variety of cancerous cells. Administration of 100 ng GcMAF/human results in the maximal activation of systemic macrophages. When nonanemic prostate and breast cancer patients (total of 36 patients) were treated with 14–25 weekly administrations of GcMAF (100 ng/week), all cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of tumors. doi:10.1016/j.clim.2007.03.512 Treatment of HIV-infected Patients with Vitamin D-binding Protein Derived Macrophage Activating Factor (GcMAF) Eradicates HIV-Infection Nobuto Yamamoto, Director, Socrates Institute for Therapeutic Immunology, Philadelphia, PA, Masumi Ueda, Immunology, Chief, Microbiology, Philadelphia, PA, Charles Benson, Head, Infectious Diseases, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA Serum vitamin D-binding protein (known as Gc 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 serum α-N-acetylgalactosaminidase (Nagalase) secreted from HIV-infected cells. Since Nagalase is the intrinsic component of gp120, serum Nagalase activity is the sum of enzyme activities expressed in both HIV virions and envelope proteins released from HIVinfected cells. Because of Nagalase being an HIV viral protein and immunogenic, serum Nagalase was already complexed with anti-HIV immunoglobulin G (IgG) in patient blood stream. These antibodies, however, were largely not neutralizing antibodies. The IgG-bound viral proteins retained Nagalase activity that deglycosylates Gc protein. Therefore, macrophages of HIV-infected patients having deglycosylated Gc protein cannot be activated, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage activating factor (termed GcMAF), which produces no side effect in humans. Macrophages activated by administration of GcMAF (100 ng/patient) develop a large amount of Fc receptors as well as enormous variation of receptors that recognize IgG bound and unbound HIV virions. Thus, macrophages activated by GcMAF preferentially phagocytize IgG-bound HIV virions via Fc receptor mediation. Cells latently infected with HIV are unstable and spontaneously release the virions at a high rate. After less than 18 weekly administrations of 100 ng GcMAF for twenty-one nonanemic patients, they exhibited low serum Nagalase activities equivalent to healthy controls, indicating eradication of HIV infection.