Intratumor BCG administration eradicates local as well as metastasized tumors (e.g., skin cancer). Administration of BCG into noncancerous tissues, however, results in no effect on the tumors. Inflammation induced by BCG in normal tissues releases lysophospholipids that activate macrophages. Because cancerous tissues contain alkylphospholipids, BCG-induced inflammation of cancerous tissues produces alkyl-lysophospholipids and alkylglycerols that activate macrophages approximately 400 times more effective than lysophospholipids, implying that highly activated macrophages are tumoricidal. Inflammation-primed macrophage activation is the principal macrophage activation process that requires serum Gc protein (known as vitamin D-binding protein) and participation of B and T lymphocytes. A trisaccharide composed of N-acetylgalactosamine with dibranched galactose and sialic acid termini at 420 threonine residue of Gc protein is hydrolyzed by the β-galactosidase (Bgl) of inflammation-primed B cells and the Neu-1 sialidase of T cells to yield the macrophage activating factor (MAF), the protein with N-acetylgalactoamine as the remaining sugar. Thus, Gc protein is the precursor for the principal MAF. However, the MAF precursor activity of serum Gc protein of cancer patients was lost or reduced because Gc protein is deglycosylated by serum α-N-acetylgalactosaminidase (Nagalase) secreted from cancerous cells. Thus, serum Nagalase activity is proportional to tumor burden and serves as an excellent prognostic index. Deglycosylated serum Gc protein can not be converted to MAF, leading to immunosuppression. Stepwise treatment of purified serum Gc protein with immobilized β-galactosidase and sialidase generates probably the most potent MAF (termed GcMAF) ever discoverd that produces no side effect in humans. Intramuscular administration of 100 ng GcMAF activates systemic macrophages at maximal level with 100-fold increased ingestion index and 30-fold increased superoxide generating capacity in 6 hrs. These activated macrophages developed an enormous variation of receptors that recognize cell surface abnormality (known as tumor associated antigen, TAA) of a variety of cancer cells and become tumoricidal to a variety of cancers indiscriminately. When those cancer patients bearing breast, prostate, colorectal, stomach, liver, lung, esophagus, kidney, bladder, uterus or ovarian cancer, or melanoma, fibrosarcoma, leukemia, glioblastoma or mesothelioma were intramuscularly administered with 100 ng GcMAF/week, their tumors were eradicated in 16 – 54 weeks which is roughly proportional to their original tumor burden. The curative rate of adenocarcinomas is a biphasic pattern due to a mixture of highly undifferentiated and differentiated tumor cells while the curative rate of all other cancer types is linear.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5531. doi:10.1158/1538-7445.AM2011-5531