Globulin Component Macrophage Activating Factor (Gc-MAF) Immunotherapy Update


In our very first BRMI e-Journal, we featured an article on GC-MAF and its therapeutic potential. In the past two years, more research has come to light as well as several excellent commercial sources of the product. This article is an update of current immunotherapy practices using GcMAF.

In review, the immune system consists of a multitude of cells and cell lines that communicate with one another through specific messenger substances.

Immunotherapy uses cells, messenger substances, and molecules to trigger a reaction in the immune system. It employs known antibodies, complement proteins, and cytokines - as well as metabolites of the vitamin D axis. Gc protein, also called vitamin D binding protein, is an abundant glycoprotein found in human blood serum as well as in other body fluids and organs.

Vitamin D Binding Protein (VDBP), also called Gc Protein

Vitamin DBP is produced in our body, mainly in the liver, especially when we are exposed to the sun. This binding protein binds to 25 (OH) vitamin D in our body for transport and storage, and plays numerous other important functions. Vitamin DBP activates macrophages through N-Acetylgalactosamine (GaINAc) - modified Gc Protein.1

Vitamin D-binding protein, the precursor protein for the macrophage-activating factor (MAF), is abundant in the serum because Gc protein circulates in remarkably high concentration (250–350 μg ml) in the bloodstream. Only 5% of Gc protein carries 25-hydroxyvitamin D3, which is a reservoir form of vitamin D. Gc protein has a strong affinity for 25-hydroxyvitamin D3, but a weak affinity for calcitriol.

Liver diseases, nephrotic syndrome, malnutrition, septic shock, and trauma is characterized by low plasma vitamin DBP concentrations, due to a diminished synthesis rate or an excessive protein loss/consumption.

Vitamin D

The body uses vitamin D in almost three thousand genes, many of which play a crucial role in immune system function. Currently, vitamin D deficiency is a global health problem. With all the medical advances of the century, vitamin D deficiency is still epidemic. It is estimated that over a billion people worldwide are vitamin D deficient or insufficient.2 Yet no international health organization or governmental body has declared a health emergency to warn the public about the urgent need of achieving sufficient vitamin D blood levels.3

Vitamin D has important functions beyond those of calcium and bone homeostasis which include modulation of the innate and adaptive immune responses. Deficiency in vitamin D is associated with increased autoimmunity as well as an increased susceptibility to infection. Vitamin D3 deficiency can result in obesity, diabetes, hypertension, depression, fibromyalgia, chronic fatigue syndrome, osteoporosis and neuro-degenerative diseases including Alzheimer’s disease. Vitamin D deficiency may even contribute to the development of cancers, especially breast, prostate, and colon cancers. Findings also indicate that inadequate levels of vitamin D may play a role in the etiology of autism.4

GcMAF Biochemistry

Inflammation results in the hydrolysis of terminal galactose and sialic acid of the Gc protein and this is mediated by membrane-bound β-galactosidase present on activated B-cells and sialidase on T-cells to produce Gc protein-derived macrophage-activating factor (GcMAF). GcMAF has been shown to possess several biological activities, such as macrophage activation via superoxide generation5, 6, phagocytic activation7, an anti-angiogenesis effect8, 9, and antitumor activities.10, 11, 12

GcMAF activates tumoricidal macrophages against a variety of cancers. 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. This enzymatic transformation is significantly stimulated by T and B lymphocytes and results, among other things, in a striking increase in activity levels of the macrophages.

As an essential component of the innate immune system, macrophages are phagocytic cells that multiply in response to an infection within the body. Macrophages distinguish, overwhelm, and obliterate pathogens, cancer cells, and foreign substances. These macrophages also circulate cytokines and eliminate cellular debris and cells that have undergone apoptosis. As such, macrophages act as a first-line or primary defense against intruders as they migrate to and circulate within almost every tissue, patrolling for pathogens and eliminating dead cells. They also direct other types of white blood cells, especially lymphocytes.