Angiogenesis is the process by which new blood vessels are formed. It is highly regulated during embryogenesis, nut neovascularization becomes excessive in pathological states such as arthritis, diabetic retinopathy, atherosclerosis and cancer. Tumors need angiogenesis for growth beyond the size of a few millimeters. This paper will look at the research studies to date using CM101 to inhibit angiogenesis in tumors.
CM101 is a complex bacterial polysaccharide exotoxin (molecular weight 300,000) isolated from culture supernatants of GBS (group B beta-hemolytic streptococcus) , previously described as GBS toxin (2). It is recovered from culture supernatants of GBS3 from infants who died of early onset septicemia. CM101 is associated with the often-fatal inflammation induced in the pulmonary neovasculature of human neonates (3). It is currently in clinical development as an anti-neovascularization agent in cancer patients and has shown encouraging results.
CM101 induces neovascular inflammation in tumors (1:365), and inhibits tumor growth and increases longevity through induction of an inflammatory response focused on tumor neovasculature resulting in vasodilation, endothelial cell damage, tumor cell necrosis, invasion of lymphocytes and monocytes, and capillary thrombosis (2). In selected animal tumors, CM101 has been shown to bind to malignant neovascular endothelium and induce a rapid and severe local inflammatory response characterized by leukocyte chemotaxis and tumor infiltration, small blood vessel coagulation and destruction, and tumor necrosis and hemorrhage (1:370).
CM101 was infused intravenously into tumor-bearing mice in picomole amounts, and was shown to bind to tumor neovasculature which activates complement by the alternative pathway (3). This caused neovasculitis, infiltration of inflammatory cells, tumor regression and ablation. Hellerqvist et al (3) infused CM101 or Dextran intravenously into tu...