GcMAF: vitamin D-binding protein-derived macrophage-activating factor

[Rich66]

Cancer Immunol Immunother. 2008 Jul;57(7):1007-16.
Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF.

Yamamoto N, Suyama H, Nakazato H, Yamamoto N, Koga Y.
Division of Cancer Immunology and Molecular Immunology, Socrates Institute for Therapeutic Immunology, 1040, 66th Ave, Philadelphia, PA 19126-3305, USA. nobutoyama@verizon.net
Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of purified Gc protein with immobilized beta-galactosidase and sialidase generated the most potent macrophage-activating factor (GcMAF) ever discovered, but it produces no side effect in humans. Macrophages treated with GcMAF (100 microg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried significant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activities of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is proportional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indicating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Nagalase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.

PMID: 18058096 [PubMed - indexed for MEDLINE]

slide presentation given by Dr. Yamamoto


Previous research:
Immunology and Cell Biology (1998) 76, 237–244; doi:10.1046/j.1440-1711.1998.00748.x
Structurally well-defined macrophage activating factor derived from vitamin D₃-binding protein has a potent adjuvant activity for immunization

Nobuto Yamamoto^1,2 and Venkateswara R Naraparaju¹

1. ¹ Laboratory of Cancer Immunology and Molecular Biology, Albert Einstein Cancer Center and
2. ² Socrates Institute for Therapeutic Immunology, Philadelphia, Pennsylvania, USA

Correspondence: N Yamamoto, Albert Einstein Cancer Center, Korman Research Pavilion B-31, 5501 Old York Road, Philadelphia, PA 19141, USA.
Received 13 March 1998; Accepted 23 March 1998.

Top of pageAbstract

Freund's adjuvant produced severe inflammation that augments development of antibodies. Thus, mixed administration of antigens with adjuvant was not required as long as inflammation was induced in the hosts. Since macrophage activation for phagocytosis and antigen processing is the first step of antibody development, inflammation-primed macrophage activation plays a major role in immune development. Therefore, macrophage activating factor should act as an adjuvant for immunization. The inflammation-primed macrophage activation process is the major macrophage activating cascade that requires participation of serum vitamin D₃-binding protein (DBP; human DBP is known as Gc protein) and glycosidases of B and T lymphocytes. Stepwise incubation of Gc protein with immobilized -galactosidase and sialidase efficiently generated the most potent macrophage activating factor (designated GcMAF) we have ever encountered. Administration of GcMAF (20 or 100 pg/mouse) resulted in stimulation of the progenitor cells for extensive mitogenesis and activation of macrophages. Administration of GcMAF (100 pg/mouse) along with immunization of mice with sheep red blood cells (SRBC) produced a large number of anti-SRBC antibody secreting splenic cells in 2–4 days. Thus, GcMAF has a potent adjuvant activity for immunization. Although malignant tumours are poorly immunogenic, 4 days after GcMAF-primed immunization of mice with heat-killed Ehrlich ascites tumour cells, the ascites tumour was no longer transplantable in these mice.


Related discussion on outside the main approaches and delays in adoption: http://prostatecancerinfolink.net/20...ic-mainstream/

By the way, I have a friend in Philly who I sent out to track him down. I spoke with him on the phone last November.