Tumor necrosis therapy antibody interleukin-2 fusion protein elicits prolonged and targeted antitumor effects in vivo.

Abstract

Interleukin-2 (IL-2) is one of the most successful cytokines applied in tumor immunotherapy because of its ability to stimulate potent cellular immune response. The life-threatening toxicity of vascular leak syndrome (VLS) associated with the high-dose IL-2 treatment regimen has limited its use in tumor immunotherapy. To reverse this situation, a tumor-targeted fusion protein, recombinant human TNT-IL2 (rhTNT-IL2), was generated with both the cytokine activity of IL-2 and the tumor-targeting ability of TNT antibody. TNT is a human tumor necrosis therapy monoclonal antibody capable of binding intracellular antigens which are accessible and abundant in necrotic regions of tumors. The immunotherapeutic potential of this fusion protein was tested in murine melanoma and lung cancer models, and tumor-bearing mice showed satisfied tumor regressions after rhTNT-IL2 immunotherapy. Immunohistochemical study showed a distinct penetration of IL-2 in tumors in mice treated with rhTNT-IL2, indicating its evident tumor-targeting activity. Moreover, the rhTNT-IL2 was well tolerated in cynomolgus monkeys in a 12-week long-term repeated toxicity study. These studies indicate that the targeting of IL-2 to necrotic areas of tumors might be a new approach for the immunotherapy of solid tumors.

• Authors: Li Ye, Jiajun Fan, Xunlong Shi, Qun Tao, Dan Ye, Zongshu Xian, Xian Zeng, Yubin Li, Meiqing Feng, Dianwen Ju
• Journal: Applied microbiology and biotechnology (Appl Microbiol Biotechnol) Vol. 98 Issue 9 Pg. 4053-61 (May 2014) ISSN: 1432-0614 [Electronic] Germany
• PMID: 24276620 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antineoplastic Agents
• Biological Products
• IL2 protein, human
• Interleukin-2
• Recombinant Fusion Proteins
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Antibodies, Monoclonal (administration & dosage, genetics)
• Antineoplastic Agents (administration & dosage)
• Biological Products (administration & dosage)
• Disease Models, Animal
• Immunotherapy (methods)
• Interleukin-2 (administration & dosage, genetics)
• Lung Neoplasms (drug therapy)
• Melanoma (drug therapy)
• Mice
• Recombinant Fusion Proteins (administration & dosage, genetics)
• Treatment Outcome
• Tumor Necrosis Factor-alpha (administration & dosage, genetics)