ANGIOGENIN ANTAGONISTS PREVENT TUMOR-GROWTH IN-VIVO

A noncytotoxic neutralizing monoclonal antibody (mAb), 26-2F, to human angiogenin (Ang), a potent inducer of neovascularization, has been re ported to prevent or delay the establishment of HT-29 human tumor xeno grafts in athymic mice. In the present study the tumor model was modif ied to increase sensitivity to Ang antagonists to facilitate further i nvestigations and comparisons of their capacity to inhibit tumor growt h. An increase in the percentage of tumor-free mice from 10-25% to 65% is observed in this modified model after treatment with mAb 26-2F. An additional neutralizing mAb, 36u, that interacts with a different epi tope on Ang similarly prevents the appearance of tumors, both alone an d in combination with mAb 26-2F. In those tumors that develop in mice treated with these agents, the number of vascular elements is reduced. Actin, an Ang antagonist that unlike the mAbs binds both human and mo use Ang, also prevents the establishment of tumors while exhibiting no toxic effects at daily doses >50 times the molar amount of circulatin g mouse Ang. Ang antagonists also inhibit the appearance of tumors der ived from two other Ang-secreting human tumor cell lines-i.e., A549 lu ng adenocarcinoma and HT-1080 fibrosarcoma. These results demonstrate that inhibition of the action of Ang is an effective therapeutic appro ach for the treatment of malignant disease.