title: Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF).
abstract: Serum vitamin D3-binding protein (Gc protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc protein of breast cancer patients was lost or reduced because Gc protein was deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to tumor burden. The deglycosylated Gc protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc protein with immobilized beta-galactosidase and sialidase generated probably the most potent macrophage activating factor (termed GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with GcMAF (100 pg/ml) are highly tumoricidal to mammary adenocarcinomas. Efficacy of GcMAF for treatment of metastatic breast cancer was investigated with 16 nonanemic patients who received weekly administration of GcMAF (100 ng). As GcMAF therapy progresses, the MAF precursor activity of patient Gc protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to tumor burden, the time course progress of GcMAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg protein. After about 16-22 administrations (approximately 3.5-5 months) of GcMAF, these patients had insignificantly low serum enzyme levels equivalent to healthy control enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg protein, indicating eradication of the tumors. This therapeutic procedure resulted in no recurrence for more than 4 years.
authors.affiliation: Division of Cancer Immunology and Molecular Biology, Socrates Institute for Therapeutic Immunology, Philadelphia, PA 19126-3305, USA. nobutoyama@verizon.net
authors.forename: Nobuto
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Suyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamamoto
authors.forename: Naofumi
authors.initials: N
authors.lastname: Ushijima
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000628:therapy*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014809:Vitamin D-Binding Protein / Q000737:chemistry* / Q000378:metabolism; D048809:alpha-N-Acetylgalactosaminidase / Q000378:metabolism
chemical_list: D016215:Macrophage-Activating Factors; D014809:Vitamin D-Binding Protein; C101908:vitamin D-binding protein-macrophage activating factor; D048809:alpha-N-Acetylgalactosaminidase; D013755:Tetradecanoylphorbol Acetate