Immunotherapy of metastatic colorectal cancer with vitamin D-binding protein-derived macrophage-activating factor, GcMAF

Serum vitamin D binding protein (Gc protein) is the precursor for the principal macrophage-activating factor (MAF). The MAF precursor activity of serum Gc protein of colorectal cancer patients was lost or reduced because Gc protein is deglycosylated by serum -N-acetyl- galactosaminidase (Nagalase) secreted from cancerous cells. Deglycosylated Gc protein cannot be converted to MAF, leading to immunosuppression. Stepwise treatment of puriWed Gc protein with immobilized -galactosidase and sialidase generated the most potent macrophage- activating factor (GcMAF) ever discovered, but it produces no side eVect in humans. Macrophages treated with GcMAF (100 pg/ml) develop an enormous variation of receptors and are highly tumoricidal to a variety of cancers indiscriminately. Administration of 100 nanogram (ng)/ human maximally activates systemic macrophages that can kill cancerous cells. Since the half-life of the activated macrophages is approximately 6 days, 100 ng GcMAF was administered weekly to eight nonanemic colorectal cancer patients who had previously received tumor-resection but still carried signiWcant amounts of metastatic tumor cells. As GcMAF therapy progressed, the MAF precursor activi- ties of all patients increased and conversely their serum Nagalase activities decreased. Since serum Nagalase is pro- portional to tumor burden, serum Nagalase activity was used as a prognostic index for time course analysis of GcMAF therapy. After 32-50 weekly administrations of 100 ng GcMAF, all colorectal cancer patients exhibited healthy control levels of the serum Nagalase activity, indi- cating eradication of metastatic tumor cells. During 7 years after the completion of GcMAF therapy, their serum Naga- lase activity did not increase, indicating no recurrence of cancer, which was also supported by the annual CT scans of these patients.