A group B streptococcus (GBS) isolated from human neonates diagnosed with
sepsis and respiratory distress ("early-onset disease") produces a
polysaccharide exotoxin (
GBS toxin) that, when infused in sheep, causes lung pathophysiology similar to that seen in humans. Histological studies have demonstrated that
GBS toxin induces a strong inflammatory response in the lung, with
pulmonary sequestration of granulocytes and extensive capillary endothelial damage. The susceptibility of humans to
GBS toxin is age-dependent and limited to about 4 days after birth. It is rarely evident thereafter. This suggests that the binding of
GBS toxin to the target endothelium occurs via specific components in the developing lung endothelial cells of the newborn that are later lost. We report here that
GBS toxin can also bind to developing endothelium associated with
neoplasia and induce an inflammatory response.
GBS toxin was shown by immunohistochemistry to bind to capillary endothelium of human
large-cell carcinomas. In nude mice bearing human
tumor xenografts, intravenously administered
GBS toxin caused
tumor necrosis and hemorrhagic lesions, and substantially inhibited the rate of growth of the
tumors. In BALB/c mice bearing Madison lung
tumors,
GBS toxin induced an inflammatory response resulting in marked changes in
tumor morphology, including vasodilation, endothelial and
tumor cell
necrosis, invasion of lymphocytes and macrophages, and capillary
thrombosis. In these
tumor models, no evidence of toxicity to the vasculature of other tissues was observed. The reported pathophysiology of GBS in human neonates, the lack of disease in non-neonates colonized with GBS, and these results suggest that
GBS toxin may have potential as a well tolerated agent in
cancer therapy of some human
tumors.