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Intratumor BCG administration can eradicate local as well as metastasized cancerous cells, suggesting development of immunity against the tumors. Administration of BCG into noncancerous tissues, however, results in no significant effect on the tumors. BCG-induced inflammation in noncancerous tissues releases lysophospholipids that efficiently activate macrophages. Because cancerous tissues contain alkylphospholipids, BCG-induced inflammation of cancerous tissue produces alkyl-lysophospholipids and alklglycerols that activate macrophages with approximately 400 times more efficiently than lysophospholipids (Cancer Res 48: 6044-9, 1988). These results imply that highly activated macrophages can kill cancerous cells. Inflammation-primed macrophage activation process is the principal macrophage activation cascade that requires serum vitamin D-binding protein (known as Gc protein) and participation of B and T lymphocytes. Stepwise hydrolysis of Gc protein with β-galactosidase of inflammation-primed B cells and sialidase of T cells yields a potent macrophage activating factor (MAF). Thus, Gc protein is the precursor for the principal MAF. However, the MAF precursor of Gc protein of cancer patients was lost or reduced because Gc protein is glycocylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Stepwise treatment of highly purified Gc protein with immobilized β-galactosidase and sialidase generated the most potent macrophage activating factor (GcMAF) ever discovered which produces no side effect in humans. Administration of 10 pg GcMAF per mouse and 100 ng GcMAF per human results in the maximal activation of macrophages, which develop enormous variation of receptors. When human macrophages were treated in vitro with 100 pg GcMAF for 3 hrs, the macrophages were highly activated and can bind a variety of cancerous cells. Because cancer cells are too big to be phagocytized, macrophage membrane spreads over the cancer cell. These attached macrophage membrane secretes superoxide and lytic enzymes. Trypan blue began penetrating from the attached site and continued to spread the entire cells. Time course study of cell death was performed with effector/target ratio of 3. In 4 hrs, 51% of prostate cancer cells LNCaP and 60% of breast cancer cells MDA-MB-231 were killed. In 18 hrs, 82% of LNCaP cells and 86% of MDA cells were killed. When prostate, breast, colon and lung cancer patients were treated with less than 25 weekly administrations of 100 ng GcMAF, the majority of cancer patients, excluding advanced, exhibited healthy control levels of the serum Nagalase activity, indicating eradication of tumors. These curative GcMAF therapy developed antibodies against tumors.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]