Angiogenesis

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 an

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e peak responses and times for the first nine patients varied depending on the cytokine measured. Peak responses usually decreased following the second and third treatments. IL-1a and Il-2 were not measurable in the system used. Interferon, bFGF and Rantes levels increased to peak eight hours after treatment and higher levels were obtained in subsequent treatments. The results indicated that vascular and cellular inflammatory reactions occurred when cancer patients were treated with CM101 and support its use in treating cancer patients. Thurman et al (7:549-553) developed a technique for implanting small numbers of tumor cells in the ear skin of mice. This allowed macroscopic examination of the tumor and its supporting blood vessels as it reaches the 10,000 cell size and greater. Treatments were monitored for effects on small "metastatic-like" tumor nodules by direct observation and by histological examination. Inflammatory changes were indicated by increased numbers of polymorphonuclear leukocytes (PMN) adjacent to and marginating within thin-walled blood vessels and within the tumor tissue. PMNs were seen in the process of migrating through venules and enlarged capillaries, each with prominent endothelial cells.

Category: Medical - A