Efficient growth inhibition of ErbB2-overexpressing tumor cells by anti-ErbB2 ScFv-Fc-IL-2 fusion protein in vitro and in vivo.

Abstract

AIM:

To investigate the antitumor activities of an anti-ErbB2 scFv-Fc-interleukin 2 (IL-2) fusion protein (HFI) in vitro and in vivo.

METHODS:

Fusion protein HFI was constructed. The efficacy of HFI in mediating tumor cell lysis was determined by colorimetric lactate dehydrogenase release assays. The antitumor activity of HFI was evaluated in tumor xenograft models.

RESULTS:

The fusion protein was folded as a homodimer formed by covalently linking Fc portions and it retained ErbB2 specificity and IL-2 biological activity. HFI mediated antibody-dependent cell-mediated cytotoxicity (ADCC) at low effector-to-target ratios in vitro and improved the therapeutic efficacy of IL-2 in experiments in vivo.

CONCLUSION:

The genetically-engineered anti-ErbB2 scFv-Fc-IL-2 fusion protein exhibited high efficiency both in mediating ADCC in vitro and significant antitumor activity in tumor xenograft models.

• Authors: Ming Shi, Ling Zhang, Hong-Tao Gu, Feng-Qin Jiang, Lu Qian, Ming Yu, Guo-Jiang Chen, Qun Luo, Bei-Fen Shen, Ning Guo
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 28 Issue 10 Pg. 1611-20 (Oct 2007) ISSN: 1671-4083 [Print] United States
• PMID: 17883948 (Publication Type: Journal Article)

Chemical References

• Immunoglobulin Fragments
• Immunoglobulin G
• Immunoglobulin Variable Region
• Interleukin-2
• Recombinant Fusion Proteins
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Animals
• Antibody-Dependent Cell Cytotoxicity
• Cell Line, Tumor
• Female
• Humans
• Immunoglobulin Fragments (genetics, immunology, metabolism)
• Immunoglobulin G (genetics, immunology, metabolism)
• Immunoglobulin Variable Region (genetics, immunology, metabolism)
• Interleukin-2 (genetics, immunology, metabolism)
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovarian Neoplasms (immunology, pathology, prevention & control)
• Receptor, ErbB-2 (genetics, immunology, metabolism)
• Recombinant Fusion Proteins (genetics, immunology, pharmacology)
• Xenograft Model Antitumor Assays