GcMAF (or Gc protein-derived macrophage activating factor) is a protein produced by modification of vitamin D-binding protein. [1] It has been falsely promoted as a treatment for various medical conditions, but claims of its benefits are not supported by evidence.
Once proclaimed a 'magic protein' capable of curing cancer, GcMAF has been proven ineffective. The case sheds light on how far scammers are willing to go to exploit desperate cancer patients and their families for financial gain.
Public warning issued by the Anticancer Fund [2]
Biochemically, GcMAF results from sequential deglycosylation of the vitamin D-binding protein (the Gc protein), which is naturally promoted by lymphocytes (B and T cells). [3] The resulting protein may be a macrophage activating factor (MAF). [3] MAFs are lymphokines that control the expression of antigens on the surface of macrophages, and one of their functions is to make macrophages become cytotoxic to tumors. [4]
Since around 2008, GcMAF has been promoted as a cure for cancer, [5] HIV, [6] autism [7] and other conditions. [8]
Three out of four of the original studies authored by Yamamoto (published between 2007 and 2009) were retracted by the scientific journals in which they were published in 2014, officially due to irregularities in the way ethical approval was granted. [6] [9] [10] [11] Retraction reasons also included methodological errors in the studies. [12] [13] The integrity of the research, conducted by Nobuto Yamamoto and colleagues, that originally prompted claims regarding cancer and HIV has been questioned. [5] [2]
The UK Medicines and Healthcare products Regulatory Agency [8] and Cancer Research UK has warned the public about spurious claims of clinical benefits, misleadingly based on reduced levels of the alpha-N-acetylgalactosaminidase enzyme (also known as nagalase), whose production might be increased in many cancers. [5]
In 2014 the Belgian Anticancer Fund communicated serious concerns about published studies on GcMAF by Yamamoto and colleagues. [2]
In 2015 the UK Medicines and Healthcare products Regulatory Agency (MHRA) closed a factory in Milton, Cambridgeshire owned by David Noakes' company Immuno Biotech that manufactured GcMAF for cancer treatment. [14]
In September 2018 Noakes pleaded guilty in UK to manufacturing a medicinal product without a manufacturer's licence, selling or supplying medicinal products without market authorisation, and money laundering, [15] and sentenced to 15 months of jail. [16] In April 2021 Noakes pleaded guilty in France to manufacturing and selling fake medicinal products and cosmetics by Internet and sentenced to 4 years of jail. [17]
A 2019 Business Insider report detailed the activities of Amanda Mary Jewell, who sold GcMAF for years as a(n unlicensed) cure for several medical conditions, including cancer and autism. [18] Jewell is not a medical doctor. [19]
Gc protein-derived macrophage-activating factor (GcMAF).
GcMAF initially conceptualized by Nobuto Yamamoto in 1991, [20] has been researched as a possible cancer treatment. [21] Previous research efforts involved the isolation of Gc protein (1f1f subtype) from human serum through an affinity column modified with 25-hydroxyvitamin D3. GcMAF was enzymatically derived from the isolated Gc protein. [22] [23]
The 2nd and 3rd generation GcMAF were developed by the Japanese organizations which hold the patents: in the USA (2014, 2016, 2017), [24] [25] [26] Japan (2015), [27] the EU (2016), [28] Australia (2016), [29] Israel (2018).
Macrophages are a type of white blood cell of the innate immune system that engulf and digest pathogens, such as cancer cells, microbes, cellular debris, and foreign substances, which do not have proteins that are specific to healthy body cells on their surface. This process is called phagocytosis, which acts to defend the host against infection and injury.
Cancer immunotherapy (immuno-oncotherapy) is the stimulation of the immune system to treat cancer, improving the immune system's natural ability to fight the disease. It is an application of the fundamental research of cancer immunology (immuno-oncology) and a growing subspecialty of oncology.
Cluster of differentiation 40, CD40 is a type I transmembrane protein found on antigen-presenting cells and is required for their activation. The binding of CD154 (CD40L) on TH cells to CD40 activates antigen presenting cells and induces a variety of downstream effects.
The nuclear receptor coactivator 2 also known as NCoA-2 is a protein that in humans is encoded by the NCOA2 gene. NCoA-2 is also frequently called glucocorticoid receptor-interacting protein 1 (GRIP1), steroid receptor coactivator-2 (SRC-2), or transcriptional mediators/intermediary factor 2 (TIF2).
α-N-acetylgalactosaminidase is a glycoside hydrolase from bacteria and animals, also known as nagalase.
Vitamin D-binding protein (DBP), also/originally known as gc-globulin, is a protein that in humans is encoded by the GC gene. DBP is genetically the oldest member of the albuminoid family and appeared early in the evolution of vertebrates.
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons.
Transcription factor Maf also known as proto-oncogene c-Maf or V-maf musculoaponeurotic fibrosarcoma oncogene homolog is a transcription factor that in humans is encoded by the MAF gene.
Transcription factor MafG is a bZip Maf transcription factor protein that in humans is encoded by the MAFG gene.
Cluster of Differentiation 276 (CD276) or B7 Homolog 3 (B7-H3) is a human protein encoded by the CD276 gene.
OX-2 membrane glycoprotein, also named CD200 is a human protein encoded by the CD200 gene. CD200 gene is in human located on chromosome 3 in proximity to genes encoding other B7 proteins CD80/CD86. In mice CD200 gene is on chromosome 16.
Transcription regulator protein BACH2 is a protein that in humans is encoded by the BACH2 gene. It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer and a bZip_Maf domain at the C-terminus.
Transcription factor MafK is a bZip Maf transcription factor protein that in humans is encoded by the MAFK gene.
Transcription factor MafF is a bZip Maf transcription factor protein that in humans is encoded by the MAFF gene.
A macrophage-activating factor (MAF) is a lymphokine or other receptor based signal that primes macrophages towards cytotoxicity to tumors, cytokine secretion, or clearance of pathogens. Similar molecules may cause development of an inhibitory, regulatory phenotype. A MAF can also alter the ability of macrophages to present MHC I antigen, participate in Th responses, and/or affect other immune responses.
Polysaccharide-K is a protein-bound polysaccharide isolated from the mycelium of Trametes versicolor.
Sonodynamic therapy (SDT) is a noninvasive treatment, often used for tumor irradiation, that utilizes a sonosensitizer and the deep penetration of ultrasound to treat lesions of varying depths by reducing target cell number and preventing future tumor growth. Many existing cancer treatment strategies cause systemic toxicity or cannot penetrate tissue deep enough to reach the entire tumor; however, emerging ultrasound stimulated therapies could offer an alternative to these treatments with their increased efficiency, greater penetration depth, and reduced side effects. Sonodynamic therapy could be used to treat cancers and other diseases, such as atherosclerosis, and diminish the risk associated with other treatment strategies since it induces cytotoxic effects only when externally stimulated by ultrasound and only at the cancerous region, as opposed to the systemic administration of chemotherapy drugs.
Joyoti Basu is an Indian biochemist, cell biologist and a senior professor at the Bose Institute. Known for her studies on the membrane structure of red blood cells, Basu is an elected fellow of all three major Indian science academies, namely the National Academy of Sciences, India, the Indian Academy of Sciences and the Indian National Science Academy, as well as the Indian Society for Chemical Biology. The Department of Biotechnology of the Government of India awarded her the National Bioscience Award for Career Development, one of the highest Indian science awards, for her contributions to biosciences in 2002.
Sunil Kumar Manna is an Indian immunologist and the head of the immunology lab of the Centre for DNA Fingerprinting and Diagnostics. He is known for his studies on cell signaling and apoptosis. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to biosciences, in 2009.
David Noakes is a British computer consultant, businessman and politician, who founded Immuno Biotech Ltd. to promote the unproven therapy GcMAF and came last in the 2006 UKIP leadership election. He pleaded guilty to "money laundering and manufacturing, supplying and selling an unlicensed medicine" and was sentenced in November 2018 to 15 months' imprisonment.
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