Construction and characterization of a new chimeric antibody against HER2
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1
Tehran University of Medical Sciences, Department of Immunology, School of Public Health, Iran
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2
Avicenna Research Institute, ACECR, Monoclonal Antibody Research Center, Iran
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3
Tabriz University of Medical Sciences, Department of Immunology, Faculty of medicine, Iran
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4
Cancer Center Karolinska, Karolinska Hospital, Immune and Gene Therapy Lab, Sweden
Aims
HER2 proto-oncogene encodes a receptor tyrosine kinase overexpressed in a variety of solid tumors. Amplification of this gene has been shown to correlate with poor prognosis in breast cancer patients. Immunotherapy with anti-HER2 antibody has shown promising results in patients with HER2-positive breast cancer. We have recently reported characterization of a mouse monoclonal antibody (mAb) (1T0) directed against HER2, which binds to an epitope different from that recognized by Trastuzumab and specifically inhibits proliferation of tumor cells overexpressing HER2. In the present study, we report chimerization of this antibody.
Materials and Methods
The immunoglobulin variable region heavy (VH) and light (VL) chain genes of 1T0 hybridoma cells were amplified and inserted into a mammalian expression vector containing cDNA of human gamma-1 and kappa constant regions using Splice Overlap Extension (SOE) PCR. The construct was subsequently transfected in the mammalian CHO cell line and the chimeric antibody was expressed, purified and characterized by ELISA, Western blot and flow cytometry.
Results
The purified chimeric antibody specifically binds to recombinant HER2 and HER2 positive tumor cells. Binding of this antibody to tumor cells inhibited proliferation of these cells. The binding affinity of the chimeric mAb was comparable to the parental mouse mAb.
Conclusion
This chimeric anti-HER2 mAb is potentially a valuable tool for targeted immunotherapy of HER2 positive malignancies.
Keywords:
Chimeric antibody,
breast cancer,
HER2,
Monoclonal antibody,
Immunotherapy
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Adaptive Immunity
Citation:
Amiri
MM,
Shokri
F,
Jeddi-Tehrani
M,
Kazemi
T,
Bahadori
M,
Maddah
M,
Hojjat-Farsanghi
M,
Khoshnoodi
J and
Rabbani
H
(2013). Construction and characterization of a new chimeric antibody against HER2
.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00069
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Received:
08 Mar 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Prof. Fazel Shokri, Avicenna Research Institute, ACECR, Monoclonal Antibody Research Center, Tehran, Iran, fazshok@yahoo.com