More than 25 years ago, the immunologist and researcher Dr. Nobuto Yamamoto isolated and produced GcMAF (Globulin Component Macrophage Activating Factor) as an immunotherapy. Since then, studies have demonstrated that GcMAF enhances the ability of the immune system to fight pathogens and cancer cells, by enhancing macrophages and reducing alpha-NaGalase.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Accordingly, its administration has potential benefits in patients with a variety of conditions, ranging from cancer (e.g., metastatic breast, metastatic colorectal, and prostate) to HIV.13, 14, 15 Dr. Yamamoto has authored or co-authored over 50 papers on immunology. In 2014, however, three of his articles were retracted16, 17, 18, giving rise to considerable negative media around GcMAF immunotherapy. Undaunted by the retractions, Dr. Yamamoto and colleagues have continued their research, further demonstrating that GcMAF has wide application for use in many diseases by activating macrophages and stimulating the immune system. Dr. Yamamoto patented the process of preparing GcMAF by treating glycosylated human group-specific component, also known as human vitamin D-binding protein, with glycosidases in 1990 and 2015.19, 20 The manufacturing process of GcMAF is very technical. GcMAF can be made via recombinant DNA technology, by inserting a small section of DNA into the bacterium E. coli. This piece of DNA reprograms the bacterium to make GcMAF. An impurity can be introduced at any step in this multistage protein manufacturing process. Hence, there is certainly risk of product contamination. Reputable manufacturers test the final product for purity and efficacy. At the research clinic Saisei Mirai in Japan, GcMAF is tested for macrophage phagocytic activity using mouse macrophages and sheep red blood cells at the University of Tokushima, Japan. The red blood cells are opsonized, which marks them for ingestion and destruction by activated macrophages. Under the microscope this can be seen as purple areas in the clear cells. They then calculate the Phagocytosis (ingestion) Index (PI). GcMAF Methods and Timing of Administration Route of administration GcMAF is administered by subcutaneous (SC) or intramuscular (IM) injection, using a Size 26G x 1/2″ (0.45 x 13 mm) or Size 27G needle with a 2.5 ml or 1 ml syringe (single use, sterile disposable). Moreover, some doctors may administer it by intravenous infusion (drip) or by IV “push” and intratumoral (IT) injection. Another option is using a nebulizer to deliver the protein to activate macrophages in the bronchus-associated lymphoid tissue (BALT) of the lungs. Oral administration of the protein is not effective because the GcMAF protein would be destroyed by stomach hydrochloric acid and pancreatic protease enzymes. Frequency and dosage In his early published human studies, Dr. Yamamoto always used the same dose: 100 nanograms (ng) per week in a single injection. 100 nanograms (100 billionths of a gram) is an extremely small amount. Dr. Yamamoto determined that the half-life of the activation effect in an activated macrophage is approximately 6 days. Therefore, he chose a once per week interval between GcMAF doses. Saisei Mirai in Japan, however, now produces a second generation high-dose GcMAF. Their doctors inject this product IM at 0.5 ml of “high dose GcMAF” (1500 ng/0.5 ml) 2-3 times per week in an integrative approach to treating cancer. They further recommend that more frequent dosing (daily or every second day) may be safely used with more advanced stage of disease, or initially in the treatment course. In certain cases, GcMAF is administered by intravenous (IV) injection, 0.5-1.0 ml 2-3 times per week in 20 ml or more saline. Saisei Mirai doctors also use IV GcMAF in addition to the usual IM/SC injections every week on alternate days. Duration of treatment The duration of GcMAF therapy depends on the individual’s condition. Usually, with most breast cancer patients 4 to 6 months is necessary to fully activate the immunity. Maintenance is often continued with oral colostrum MAF. Monitoring GcMAF Treatment GcMAF administration must always be monitored by a physician trained in its use. Aside from the usual breast cancer tests (monitoring the effectiveness of treatments), there are two additional tests that are used. The first is the monocyte count of a white blood cell differential. Monocytes produced in the bone marrow enter the blood, then migrate to organs and tissues where they mature into macrophages. Official nomenclature further subdivides monocytes into three subsets (a topic for another day). Low monocyte count, low phagocytic activity of monocytes, low lymphocyte count, low NK cell activity, and depressed TNF-α are often observed following standard external beam chest radiation therapy or cytotoxic chemotherapy for breast cancer. This has consequences for anticancer immune competence in the weeks and months following completion of standard treatment and is why immunotherapy is so important. GcMAF therapy increases the number of monocytes as it activates macrophages. A patient’s monocyte count will generally rise in the early stages of GcMAF treatment and indicates a response to GcMAF. Normal monocyte levels are between 2% and 10% of the total differential. Upward of 6% or more is considered optimum response to GcMAF treatment. Cancers and viruses both make alpha-NaGalase. Specialized laboratories can now measure the level of nagalase in the blood. An elevated nagalase test result reveals that either cancer or a virus (or both) could be present. It has been established that nagalase activity is directly proportional to viable tumor burden; whereas decreased nagalase activity is associated with improved clinical conditions. Hence, some doctors using GcMAF treatment employ nagalase testing to determine the efficacy of the therapy. Be advised that reference ranges differ slightly depending on the laboratory. Because the measurement of this enzyme can diagnose the presence of cancerous lesions below levels detectable by other diagnostic means, nagalase testing may become a standard biomarker for early cancer detection. GcMAF Side Effects There have been no reported side effects (nor toxic reactions) from GcMAF therapy. The primary reason being that its molecular structure is bioidentical (identical to the GcMAF made by the body). So, as long as the GcMAF is pure*, there is no reason to expect any side effects. *A pure GcMAF protein contains only molecules of a single protein, and no other molecules of any kind. Impurities cause compromised effectiveness, adverse reactions, and symptoms of toxicity. Beware because there are “bootleg” or phony versions of GcMAF being manufactured that are impure, contaminated, and consequently potentially toxic. These products are often sold over the internet, and their packaging may look identical to the real product. It is best to purchase GcMAF directly from the clinics in Japan21 or Europe. These clinics usually require the patient to undergo GcMAF treatment at the clinic, and then dismiss the patient with enough product to follow up at home for several weeks. Thousands of patients over the last two decades have been treated with GcMAF in the United Kingdom, Europe and Asia (especially Japan). But many of its practitioners have faced adversity. A UK factory where GcMAF was being manufactured was closed under claims that the product “might be contaminated.” Importation of GcMAF into the UK has been halted. Big Pharma was quick to realize that GcMAF was being manufactured and sold at a fraction of the cost of other immunotherapy products. Moreover, a universal cancer cure would destroy the profitability of the highly lucrative cancer industry, and collapse the American Cancer Society, hospitals, oncology clinics and pharmaceutical companies that depend on chemotherapy revenues to stay profitable. Consequently, shipments of GcMAF into the U.S. have been confiscated, and its use has been made illegal. Astoundingly, a few U.S. doctors who had been using GcMAF, or advocating its use, were found dead under suspicious circumstances; conspiracy rumors still abound. It is estimated that at least 350 doctors in 80 countries are using GcMAF, but currently research studies are limited to Japan and parts of Europe (e.g., Germany). Big Pharma and its regulatory agencies have done much to discredit – and make unavailable – the product. The internet is full of quackery websites discrediting GcMAF and the doctors who advocate its use. It is tragic that cytotoxic chemotherapy, which has very little proven efficacy in survival time, and which produces serious (and even fatal) side effects, can be marketed to the sick and dying – but a harmless body protein, studied for over twenty-five years as a promising immunotherapy agent, is not even available for research in the U.S. For more information, click here to visit our video library. 1. Dr. Nobuto Yamamoto was born in Japan April 25, 1925. He spent his adult life researching microbiology. In 1980, Dr. Yamamoto was appointed Professor of Microbiology and Immunology at Hahnemann University School of Medicine, where he continued his research in viral evolution. His immunological studies focused on the mechanism of macrophage activation and GcMAF. When Dr. Yamamoto retired from Hahnemann University in 1990, he returned to Temple University Medical School as a Research Professor of Biochemistry and studied the tumoricidal capacity of macrophages activated by GcMAF and cancer therapy with GcMAF. In 1994, Dr. Yamamoto founded the Socrates Institute for Therapeutic Immunology, where he continues to study the therapeutic efficacy of GcMAF for a variety of cancers and HIV. 2. Yamamoto N, and Kumashiro R, Conversion of vitamin D3 binding protein (group specific component) to a macrophage activating factor by the stepwise action of ß-galactosidase of B cells and sialidase of T cells, J. lmmunol. 151 2794–2802 (1993). 3. Yamamoto N, Homma S, Haddad JG, Kowalski MA, Vitamin D3 binding protein required for in vitro activation of macrophages after alkylglycerol treatment of mouse peritoneal cells, Immunology. 74 420–424 (1991). 4. Yamamoto N, and Homma S, Vitamin D3 binding protein (group specific component) is a precursor for the macrophage-activating signal, Proc.Natl. Acad. Sci. USA 88 8539–8543 (1991).
5. Korbelik M, Naraparaju VR, Yamamoto N. The value of serum alpha-N-acetylgalactosaminidase measurement for the assessment of tumour response to radio- and photodynamic therapy.Br J Cancer. 1998 Mar; 77(6):1009-14.
6. Naraparaju VR, Yamamoto N. 1994. Roles of b-galactosidase of B lymphocytes and sialidase of T lymphocytes in inflammation primed activation of macrophages. Immunol Lett 43:143–148. 7. Yamamoto, N., and Homma, S. Vitamin D3 binding protein (group-specific component, Gc) is a precursor for the macrophage activating signal factor from lysophosphatidylcholine-treated lymphocytes.Proc. NatI. Acad. Sci. USA, 88: 8539-8543, 1991. 8. Yamamoto N, Ueda M, Benson CE. 2007. Treatment of HIV-infected patients with Gc protein-derived macrophage activating factor (GcMAF) eradicates HIV-infection. Proc 13th Int Cong Immunol. Italy: Medimond, Bologna. pp. 35–38. 9. Yamamoto N, Kumashiro R.. Conversion of vitamin D3 binding protein (Group specific component) to a macrophage activating factor by the stepwise action of b-galactosidase of B cells and sialidase of T cells. J Immunol 151:2794–2802, 1993. 10. Yamamoto N, Homma S, Millman I. 1991. Identification of the serum factor required for in vitro activation of macrophages: Role of vitamin D3 binding protein (Group specific component, Gc) in lysophospholipid activation of mouse peritoneal macrophages. J Immunol 147:273–280. 11. Nobuto Yamamoto, Masahiro Urade, Yoshihiko Koga, Nobuyuki Yamamoto, Theodor Sery and Masumi Ueda. Macrophages Activated By GCMAF Develop Enormous Variation of Receptors That Recognize and Eradicate Adenocarcinomas. Clinical Immunology, Volume 119, Supplement 1, 2006, Page S96. FOCIS 2006 Abstract Supplement – 6th Annual Meeting. 12. Yamamoto, Masahiro Urade, Yoshihiko Koga, Nobuyuki Yamamoto, Theodor Sery and Masumi Ueda. Macrophages Activated By GCMAF Develop Enormous Variation of Receptors That Recognize and Eradicate Adenocarcinomas. Nobuto 2006. 13. Thyer L. et al. GC protein-derived macrophage-activating factor decreases α-N-acetylgalactosaminidase levels in advanced cancer patients. Oncoimmunology. 2013;2(8): e25769. 14. Yamamoto N, Suyama H and Yamamoto N: Immunotherapy for prostate cancer with Gc protein-derived macrophage-activating factor, GcMAF. Transl Oncol 1: 65-72, 2008. 15. Gregory KJ, Zhao B, Bielenberg DR, Dridi S, Wu J, Jiang W, et al. (2010) Vitamin D Binding Protein-Macrophage Activating Factor Directly Inhibits Proliferation, Migration, and uPAR Expression of Prostate Cancer Cells. PLoS ONE 5(10): e13428. doi:10.1371/journal.pone.0013428 16. Yamamoto N, Suyama H, Yamamoto N and Ushijima N: Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF). Int J Cancer 122: 461-467, 2008. Retraction: Immunotherapy of metastatic breast cancer patients with vitamin D-binding protein-derived macrophage activating factor (GcMAF)’ [Int J Cancer. 2014] 17. Yamamoto N, Ushijima N and Koga Y: Immunotherapy of HIV infected patients with Gc protein-derived macrophage activating factor (GcMAF). J Med Virol 81: 16-21, 2009. – Retraction. Immunotherapy of HIV-infected patients with Gc protein-derived macrophage activating factor. [J Med Virol. 2014]
18. Yamamoto N, Suyama H, Nakazato H, Yamamoto N and Koga Y: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage activating factor, GcMAF. Cancer Immunol Immunother 57: 1007-1016, 2008. – Retraction: Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF. [Cancer Immunol Immunother. 2014] 19. http://patents.com/us-5177002.html – In vitro enzymatic conversion of glycosylated human vitamin D binding protein to a potent macrophage activating factor: Abstract: A novel, potent macrophage activating factor is prepared in vitro by treating glycosylated human group-specific component, also known as human vitamin D-binding protein, with glycosidases. Group-specific component, which is isolated from retired blood by known procedures, is thus readily converted to a highly potent macrophage activating factor. 20. http://www.freepatentsonline.com/20150361151.pdf 21. Saisei Mirai is a medical organization in Osaka, Japan, with the purpose of treating patients and developing and producing therapies, in particular immunotherapies such as GcMAF and colostrum MAF. http://www.saisei-mirai.or.jp/gan/index_eng.html.