Related Experiment Videos
Angiogenin antagonists prevent tumor growth in vivo
K A Olson1, J W Fett, T C French
1Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115.
Abstract:
A noncytotoxic neutralizing monoclonal antibody (mAb), 26-2F, to human angiogenin (Ang), a potent inducer of neovascularization, has been reported to prevent or delay the establishment of HT-29 human tumor xenografts in athymic mice. In the present study the tumor model was modified to increase sensitivity to Ang antagonists to facilitate further investigations and comparisons of their capacity to inhibit tumor growth. 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 epitope on Ang similarly prevents the appearance of tumors, both alone and 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 mouse Ang, also prevents the establishment of tumors while exhibiting no toxic effects at daily doses > 50 times the molar amount of circulating mouse Ang. Ang antagonists also inhibit the appearance of tumors derived from two other Ang-secreting human tumor cell lines--i.e., A549 lung adenocarcinoma and HT-1080 fibrosarcoma. These results demonstrate that inhibition of the action of Ang is an effective therapeutic approach for the treatment of malignant disease.
Insights
Neutralizing antibodies and actin targeting angiogenin (Ang) effectively prevent tumor growth in mice. This demonstrates that inhibiting Ang is a promising therapeutic strategy for treating malignant diseases.
Area of Science:
- Oncology
- Immunology
- Biochemistry
Background:
- Angiogenin (Ang) is a potent inducer of neovascularization.
- Ang promotes tumor growth and is implicated in malignant disease.
- Previous studies showed a neutralizing monoclonal antibody (mAb) 26-2F to Ang could delay HT-29 tumor xenografts in mice.
Purpose of the Study:
- To modify a tumor model to increase sensitivity to Ang antagonists.
- To compare the efficacy of different Ang antagonists in inhibiting tumor growth.
- To investigate the therapeutic potential of inhibiting Ang action against various human tumor cell lines.
Main Methods:
- Utilized a modified HT-29 human tumor xenograft model in athymic mice.
- Administered neutralizing monoclonal antibodies (mAbs) 26-2F and 36u targeting Ang.
- Administered Actin, an Ang antagonist with cross-species activity.
- Assessed tumor incidence, vascularity, and toxicity.
Main Results:
- The modified model showed a significant increase in tumor-free mice (65%) after treatment with mAb 26-2F.
- Both mAb 26-2F and mAb 36u, alone and in combination, prevented tumor appearance.
- Ang antagonists reduced vascularity in developing tumors and inhibited tumors from A549 and HT-1080 cell lines.
- Actin prevented tumor establishment without observable toxicity.
Conclusions:
- Inhibition of angiogenin (Ang) action is an effective therapeutic strategy for malignant diseases.
- Neutralizing antibodies and Actin demonstrate significant anti-tumor effects.
- Targeting Ang offers a promising approach for cancer treatment.