Serum
vitamin D3-binding
protein (Gc
protein) is the precursor for the principal macrophage activating factor (MAF). The MAF precursor activity of serum Gc
protein of
breast cancer patients was lost or reduced because Gc
protein was deglycosylated by serum
alpha-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Patient serum Nagalase activity is proportional to
tumor burden. The deglycosylated Gc
protein cannot be converted to MAF, resulting in no macrophage activation and immunosuppression. Stepwise incubation of purified Gc
protein with immobilized
beta-galactosidase and
sialidase generated probably the most potent macrophage activating factor (termed
GcMAF) ever discovered, which produces no adverse effect in humans. Macrophages treated in vitro with
GcMAF (100 pg/ml) are highly tumoricidal to mammary
adenocarcinomas. Efficacy of
GcMAF for treatment of metastatic
breast cancer was investigated with 16 nonanemic patients who received weekly administration of
GcMAF (100 ng). As
GcMAF therapy progresses, the MAF precursor activity of patient Gc
protein increased with a concomitant decrease in serum Nagalase. Because of proportionality of serum Nagalase activity to
tumor burden, the time course progress of
GcMAF therapy was assessed by serum Nagalase activity as a prognostic index. These patients had the initial Nagalase activities ranging from 2.32 to 6.28 nmole/min/mg
protein. After about 16-22 administrations (approximately 3.5-5 months) of
GcMAF, these patients had insignificantly low serum
enzyme levels equivalent to healthy control
enzyme levels, ranging from 0.38 to 0.63 nmole/min/mg
protein, indicating eradication of the
tumors. This therapeutic procedure resulted in no recurrence for more than 4 years.