Promising role for Gc-MAF in cancer immunotherapy: from bench to bedside - 0 views
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MAF precursor activity has also been lost or reduced after Gc-globulin treatment in some cancer cell lines
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This appears to result from the deglycosylated ɑ-N-acetylgalactosaminidase (nagalase) secreted from cancerous cells
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Nagalase has been detected in many cancer patients, but not in healthy individuals
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Studies have shown that the production of nagalase has a mutual relationship with Gc-MAF level and immunosuppression
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It has been demonstrated that serum levels of nagalase are good prognosticators of some types of cancer
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The nagalase level in serum correlates with tumor burden and it has been shown that Gc-MAF therapy progresses, nagalase activity decreases
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It has been shown that Gc-MAF can inhibit the angiogenesis induced by pro-inflammatory prostaglandin E1
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The effect of Gc-MAF on chemotaxis or activation of tumoricidal macrophages is likely the main mechanism against angiogenesis.
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Administration of Gc-MAF stimulates immune-cell progenitors for extensive mitogenesis, activates macrophages and produces antibodies. “This indicates that Gc-MAF is a powerful adjuvant for immunization.”
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Cancer cell lines do not develop into tumor genes in mouse models after Gc-MAF-primed immunization (29-31) and the effect of Gc-MAF has been approved for macrophage stimulation for angiogenesis, proliferation, migration and metastatic inhibition on tumors induced by MCF-7 human breast cancer cell line
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The protocol included: "a high dose of second-generation Gc-MAF (0.5 ml) administered twice a week intramuscularly for a total of 21 injections.”
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Yamamoto et al. showed that the administration of Gc-MAF to 16 patients with prostate cancer led to improvements in all patients without recurrence
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Inui et al. reported that a 74-year-old man diagnosed with prostate cancer with multiple bone metastases was in complete remission nine months after initiation of GcMAF therapy simultaneously with hyper T/NK cell, high-dose vitamin C and alpha lipoic acid therapy
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It has also been approved for non-neoplastic diseases such as autism (41), multiple sclerosis (42, 43), chronic fatigue syndrome (CFS) (40), juvenile osteoporosis (44) and systemic lupus erythematous (45).
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Gc-MAF has been verified for use in colon, thyroid (38), lung (39), liver, thymus (36), pancreatic (40), bladder and ovarian cancer and tongue squamous carcinoma
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Prostate, breast, colon, liver, stomach, lung (including mesothelioma), kidney, bladder, uterus, ovarian, head/neck and brain cancers, fibrosarcomas and melanomas are the types of cancer tested thus far
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weekly administration of 100 ng Gc-MAF to cancer at different stages and types showed curative effects at different follow-up times
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this treatment has been suggested for non-anemic patients
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Studies have shown that weekly administration of 100 ng Gc-MAF to cancer patients had curative effects on a variety of cancers
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Because the half-life of the activated macrophages is approximately one week, it must be administered weekly
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In vivo weekly intramuscular administration of Gc-MAF (100 ng) for 16-22 weeks was used to treat patients with breast cancer
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individuals harboring different VDR genotypes had different responses to Gc-MAF and that some genotypes were more responsive than others
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Administration of Gc-MAF for cancer patients exclusively activates macrophages as an important cell in adaptive immunity
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Gc-MAF supports humoral immunity by producing, developing and releasing large quantities of antibodies against cancer. Clinical evidence from a human model of breast cancer patients supports this hypothesis
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There is also evidence that confirms the tumoricidal role of Gc-MAF via Fc-receptor mediation
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It is likely that the best therapeutic responses will be observed when the nutritional and inflammatory aspects are taken together with stimulation of the immune system
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it should be noted that no harmful side effects of Gc-MAF treatment have been reported, even when it was successfully administered to autistic children
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The natural activation mechanism of macrophages by Gc-MAF is so natural and it should not have any side effects on humans or animal models even in cell culture
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Besides the Gc-MAF efficacy on macrophage activity, it can be a potential anti-angiogenic agent (28) and an inhibitor of the migration of cancerous cells in the absence of macrophages (47).
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Activating or modifying natural killer cells, dendritic cells, DC, CTL, INF and IL-2 have all been recommended for cancer immunotherapy
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It has been reported that nagalase cannot deglycosylate Gc-MAF as it has specificity for Gc globulin alone
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inflammation-derived macrophage activation with the participation of B and T lymphocytes is the main mechanism
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macrophages highly-activated by the addition of Gc-MAF can show tumoricidal activity
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Previous clinical investigations have confirmed the efficacy of Gc-MAF. In addition to activating existing macrophages, Gc-MAF is a potent mitogenic factor that can stimulate the myeloid progenitor cells to increase systemic macrophage cell counts by 40-fold in four days
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great review on Gc-MAF in cancer. An increase in nagalase blocks Gc-protein to Gc-MAF activity leaving the host immune system compromised.
