About GcMaf
1991
Stepwise treatment of purified serum Gc protein with immobilized β-galactosidase and sialidase generates probably the most potent MAF (macrophage activating factor) (termed GcMAF) ever discovered that produces no side effect in humans.
Nobuto Yamamoto
How?
β-galactosidase, also called lactase, beta-gal or β-gal, is a glycoside hydrolase enzyme that catalyzes the hydrolysis of β-galactosides into monosaccharides through the breaking of a glycosidic bond. β-galactosides include carbohydrates containing galactose where the glycosidic bond lies above the galactose molecule.
Selective deglycosylation of the protein has been shown to occur naturally as part of the inflammatory response. Membrane-bound b-galactosidase and sialidase of activated B- and T-lymphocytes can hydrolyze the terminal galactose and sialic acid to yield a potent macrophage activating molecule- DBP-derived macrophage activating factor, called DBP-maf.
Vitamin D Binding Protein-Macrophage Activating Factor Inhibits HCC in SCID Mice
Koichi Nonaka, M.D.,*,1 Shinya Onizuka, M.D., Ph.D.,* Hiromi Ishibashi, M.D., Ph.D.,* Yoshihiro Uto, Ph.D.,† Hitoshi Hori, Ph.D.,† Toshiyuki Nakayama, M.D., Ph.D.,‡ Nariaki Matsuura, M.D., Ph.D.,§ Takashi Kanematsu, M.D., Ph.D.,k and Hikaru Fujioka, M.D., Ph.D.*
Journal of Surgical Research 172, 116–122 (2012)
doi:10.1016/j.jss.2010.07.057
Japan
GcMAF, or Gc protein-derived Macrophage Activating Factor, is an immunotherapy developed in Japan by Saisei Mirai clinics in collaboration with researchers from the University of Tokushima. Beginning in 1992, they advanced GcMAF into a second-generation form by 2011, enhancing its concentration, stability, and activity. Produced in Saisei Mirai’s sterile Cell Processing Center, this version is 10–20 times more potent than earlier forms and has been safely administered to over 1,000 patients. It activates macrophages to combat diseases like cancer, chronic fatigue syndrome, and autism spectrum disorders. Clinical studies show minimal side effects, typically limited to mild, short-term reactions in rare cases.
NATURAL ORAL IMMUNE THERAPY – GCMAF
GcMAF (Gc Protein-derived Macrophage Activating Factor) occurs naturally in our bodies and instructs macrophages to destroy cancerous cells and foreign invaders by activating them. Macrophages (Greek: big eaters) are cells originating from monocytes, a type of white blood cell found in the body. Macrophages function in both non-specific defense (innate immunity) as well as help initiate specific defense mechanisms (adaptive immunity) of vertebrate animals.
Their role is to phagocytize (engulf and then digest) cellular debris and pathogens, either as stationary or as mobile cells. They also stimulate lymphocytes and other immune cells to respond to pathogens.
They are specialized phagocytic cells that attack foreign substances, infectious microbes and cancer cells through destruction and ingestion.
Where are macrophages found in the body? Macrophages and other phagocytes are found in the following locations in the body:
| Main location | Types of phagocytes |
| Skin * | macrophages, resident Langerhans cells, dendritic cells, mast cells |
| Gut and intestinal Peyer’s patches | macrophages |
| Lungs | macrophages, monocytes, mast cells, dendritic cells |
| Blood | neutrophils, monocytes |
| Bone marrow | macrophages, monocytes, sinusoidal cells, lining cells |
| Connective tissue | macrophages, monocytes, dendritic cells, histiocytes |
| Lymphoid tissue | macrophages, monocytes, dendritic cells |
| Spleen | macrophages, monocytes, sinusoidal cells |
| Thymus | macrophages, monocytes |
For any infectious or parasitic disease to start, it is always a requisite that the host suffer IMMUNODEFICIENCY. At the same time, infectious and parasitic diseases themselves cause additional IMMUNE SUPPRESSION and more MALNUTRITION. This immune suppression is SECONDARY to the accumulation of free radicals, especially oxidizing species, that occurs during and after infectious and parasitic diseases.
Clinical Aspects of Immunology and Biochem J.
The spleen holds 50 percent of both macrophages and monocytes. Following GcMAF treatment, the direction of blood flow to the spleen increases along with other biological components that stimulate a healthy immune system. The mouth and throat contain specific immunological lymphoid tissue highly concentrated with macrophages. Mixing colostrum powder with water and swishing it around your mouth for 15 to 20 minutes can activate macrophages and help you absorb immunoglobins sublingually. Critical neural macrophages are microglia and are found in the brain and spine. Microglia supports the immune system by defending against invasive threats to the central nervous system which create damage. Microglia is one of the central nervous system’s first lines of defense. Many substances can activate macrophages, some probiotics are able to independantly activate macrophages. Enzymes of certain strains of microorganisms contained in yogurt and kefir are able to convert milk Gc-protein into active DBP-MAF.
GcMaf in supplement form from Sasei Mirai Japan is now made from cheese whey instead of bovine colostrum. Their blood derived gc protein therapy is still available in clinic.
Remember human studies or infant studies can not be ethically done regarding the development of a human microbiome and immune system. In some rare instances specific formulas can be tried on premature infants in order to improve their chances of survival.
About GcMaf:
GcMAF is created through the enzymatic deglycosylation of the Gc protein (vitamin D-binding protein). Sequential hydrolysis by β-galactosidase and sialidase removes terminal sugar groups, leaving only the essential N-acetylgalactosamine (GalNAc) attached to Threonine 420, which is required to activate macrophages.
The Enzymatic PathwayThe Precursor (Gc Protein): The native Gc protein in human plasma contains an O-linked trisaccharide at Threonine 420 consisting of Galactose, Sialic acid, and GalNAc.Step 1: β-Galactosidase Hydrolysis: The enzyme β-galactosidase selectively targets and cleaves the terminal galactose (Gal) from the trisaccharide chain. This step serves as the common first-stage modification in generating GcMAF.
Step 2: Sialidase Hydrolysis: The enzyme sialidase subsequently cleaves the terminal sialic acid from the glycan chain.
Final Product (GcMAF): This stepwise enzymatic deglycosylation exposes the core GalNAc moiety on the protein backbone, transforming the precursor into the active Gc protein-derived macrophage-activating factor (GcMAF).
GcMAF is considered a systemic immune modulator because its effects extend far beyond simply turning on macrophages.
It acts as a signaling bridge that coordinates both the innate and adaptive immune systems, altering overall immune behavior and the tissue microenvironment.
While it is a powerful stimulant, a true “modulator” balances, directs, and adapts the immune system through several interconnected mechanisms.
1. Link to Adaptive Immunity (Antigen Presentation)Macrophages do not just destroy pathogens; they are Antigen-Presenting Cells (APCs). When GcMAF activates a macrophage, it aggressively drives phagocytosis (the engulfing of threats).The Process: The macrophage breaks down the digested tumor cells or viruses and displays their pieces (antigens) on its surface.
The Modulating Effect: This presentation “trains” and alerts T-cells and B-cells. It essentially converts a localized innate response into a widespread, highly specific adaptive immune response.
2. Cytokine Regulation and Adjuvant Activity GcMAF behaves as a potent immunological adjuvant. It triggers localized inflammation and mitogenesis (cellular division) of immune-cell progenitors. It stimulates the release of key signaling proteins (cytokines) that recruit backup forces—such as neutrophils and lymphocytes—to the site of an infection or tumor. Rather than causing a destructive, uncontrolled inflammatory storm, it optimizes the speed and accuracy of the response.
3. Modifying the Suppressive Microenvironment In chronic illnesses and aggressive cancers, the local immune system is often suppressed. Tumors recruit specific cells, like myeloid-derived suppressor cells (MDSCs) and pro-tumor M2 macrophages, to shut down immune attacks. GcMAF helps modulate this environment by: Inhibiting the synthesis of pro-tumor and immunosuppressive factors. Shifting the balance away from tissue-protective, tumor-promoting “M2” macrophage behaviors and back toward defensive “M1” behaviors.
4. Non-Immune Systemic Actions True immunomodulators often influence physiological pathways closely tied to immune health, such as blood vessel growth and cell death. GcMAF has been shown to: Inhibit Angiogenesis: It blocks the formation of new blood vessels, which tumors rely on to grow and evade immune detection. It mediates this effect by stimulating cyclic AMP (cAMP) and interacting with CD36 cell receptors.
Scavenge Extracellular Actin: In its role as the Vitamin D-binding protein, it helps clear out toxic actin filaments released by dying cells, preventing microvascular blockages and protecting surrounding tissues from inflammation.
Macrophages and Regulatory T cells (Tregs) have a deeply intertwined, reciprocal relationship.
Rather than acting as separate entities, they communicate constantly in a two-way street to regulate immune responses, promote tissue repair, and resolve inflammation. The relationship between these two critical immune cells unfolds in three primary ways:
1. Macrophages Shape Tregs
Macrophages process cellular debris and present antigens to T cells. Depending on the local environment, they directly guide T cells to become Tregs:
* Induction: When macrophages clear apoptotic (dead) cells, they secrete TGF-β. This cytokine tells helper T cells to differentiate into Tregs, shifting the immune system from an attack mode to a tolerance mode.
* Proliferation: Anti-inflammatory macrophages (often called M2 macrophages) release specific proteins that sustain and support the growth of existing Treg populations.
2. Tregs Regulate Macrophages
Once activated, Tregs act as the “brakes” of the immune system and exert profound control over macrophage behavior:
* Polarization: Tregs secrete cytokines (like IL-10 and IL-13) that reprogram pro-inflammatory macrophages (M1) into anti-inflammatory, tissue-repairing macrophages (M2).
* Efferocytosis: Tregs boost the ability of macrophages to clean up and engulf dead cells—a process known as efferocytosis.
* Lipid Reduction: In conditions like atherosclerosis, Tregs significantly reduce the ability of macrophages to accumulate cholesterol, stopping them from turning into foam cells.
3. Collaboration in Disease States
Because this relationship is built on controlling inflammation, the breakdown or hijacking of Treg-macrophage crosstalk dictates the outcome of many conditions:
* Cancer: Tumors manipulate this axis to their advantage. Tumor cells cause macrophages to adopt an M2 phenotype, which actively recruits Tregs into the tumor. Together, these two cells suppress anti-tumor immune responses, helping the cancer evade destruction.
* Autoimmune Diseases: A breakdown in communication—where Tregs fail to properly control inflammatory macrophages—can result in uncontrolled autoimmune responses, such as rheumatoid arthritis or multiple sclerosis.
* Tissue Healing: After an injury (such as a heart attack), Tregs home to the damaged tissue and quickly push macrophages to adopt a repair-oriented state, limiting scar tissue and restoring function.
Immunotherapy with GcMAF revisited - A critical overview of the research of Nobuto Yamamoto - Epub 2022
GcMAF
Yamamoto and co-workers found that activation of B cells by DDG induced a 3-fold increase of the outersurface-bound β-galactosidase. They suspected that this enhanced activity might play a role in the conversion of Gc into an activator of macrophages. They further assumed that the outersurface-bound neuraminidase (sialidase) activity of untreated T cells was also involved. This led to the idea, that in their animal studies, the known O-glycosylation of the Gc protein [18] was partly deglycosylated by β-galactosidase (of DDG-activated B cells) and sialidase (of T cells) to a Gc product, termed GcMAF.