• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5977-5981
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• 2015

Background: Worldwide, breast cancer is the most common cancer diagnosed among women and a leading cause of cancer deaths. The age of onset in Iran has become reduced by a decade for unknown reasons. Herceptin, a humanized monoclonal antibody, is a target therapy for breast cancer cells with over expression of HER2-neu receptors, but it is an expensive drug with only 20% beneficial rate of survival. This study introduces a novel approach to enhance the efficacy of this drug through immunoconjugation of the antibody to botulinum toxin. Decreasing the cost and adverse effects of the antibody were secondary goals of this study. Materials and Methods: Botulinum toxin was conjugated with Herceptin using heterobifunctional cross linkers, succinimidyl acetylthiopropionate (SATP) and sulfo-succinimidyl-4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) according to the supplier's guidelines and tested on two breast cancer cell lines: SK-BR-3 and BT-474. Toxin and Herceptin were also used separately as controls. The cytotoxicity assay was also performed using the new bioconjugate on cultured cells with Alamar blue and a fluorescence plate reader. Results: Herceptin-Toxin bioconjugation significantly improved Herceptin efficacy on both breast cancer cell lines when compared to the control group. Conclusions: Toxin-Herceptin bioconjugation can be a potential candidate with increased efficiency for treating breast cancer patients with over expression of the HER2 receptor.

• The Korea Genome Conference
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• 2004.07a
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• pp.50.2-50.2
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• 2004

• Proceedings of the Korean Society of Toxicology Conference
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• 2005.11a
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• pp.133-141
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• 2005

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2795-2798
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• 2012

Objective: This study is conducted to evaluate the effects of anti-HER-2${\times}$anti-CD3 bi-specific antibodies(BsAb) on HER-2/neuover-expressing human colorectal carcinoma cells. Methods: Growth was assessed by MTT assays after exposure of HCT-116 cells to Herceptin, anti-CD3 and BsAb antibodies. Immunocytochemistry was applied to test the HER-2 level of HCT-116. In a nude mouse model, HER-2${\times}$CD3 BsAb was combined with effector cells (peripheral blood lymph cells from normal human being) for observations on in Vivo growth of tumors. Results: Compared with the control group, using effector cells combined with anti-CD3 McAb, Herceptin or HER2${\times}$CD3 BsAb, tumor cell growth in vitro and in vivo was significantly inhibited (P<0.05), most remarkably in the HER2${\times}$CD3 BsAb case. The growth of xenografts with HER2${\times}$CD3 BsAb combined with effector cells was also significantly inhibited when compared with the anti-CD3 McAb or Herceptin groups (P<0.05). Conclusion: HER-2/neu might be a useful target for immunotherapy in colorectal carcinoma, anti-HER2${\times}$anti-CD3 BsAb exerting clear anti-tumor effects.

• Proceedings of the Korea Crystallographic Association Conference
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• 2003.11a
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• pp.9-9
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• 2003

• Proceedings of the Korean Society of Applied Pharmacology
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• 2008.04a
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• pp.77-86
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• 2008

It's been known that overexpression of the oncoprotein Her2 (eu/ErbB2), transmembrane receptor protein, occurs in human breast cancer. Her2-positive breast cancer patients who have Her2 overexpression show less therapeutic efficacy with enhanced metathesis and increased resistance to chemotherapy. So far, a humanized monoclonal antibody against Her2 protein called Herceptin is the only drug approved by Food and Drug Administration for treatment of Her2-overexpressing breast tumors. However, antibody therapy of Herceptin may not be ideal method for therapeutic intervention of Her2 protein expression. The therapeutic intervention of Her2 protein expression may be more efficiently achieved by inhibiting the expression of Her2 gene rather than by down-regulating the Her2 protein already overexpressed. Here, we found that the interaction of two proteins of ESX (an epithelial-restricted transcription factor) and DRIP130/CRSP130/Sur2 (a Ras-linked subunit of human mediator complexes) mediates the expression of Her2 gene. The association of ESX with Sur2 is mediated by a small hydrophobic face of 8-amino acid helix in ESX, suggesting that the ESX-Sur2 interaction can be a new novel target for Her2-positive cancer. The process to develop potent ESX-Sur2 interaction inhibitors targeting for Her2-positive cancer therapeutics will be discussed.

• Journal of Korean Traditional Oncology
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• v.24 no.2
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• pp.13-21
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• 2019

Objective : The purpose of this study is to report and observe effects of Traditional Korean Medicine (TKM) on stage IV metastatic breast cancer patient. Method : A right breast cancer patient diagnosed with metastatic lesions on liver, lung, spleen, multiple bones and skin on right breast April 2013. The patient received Herceptin + Docetaxel + Zometa from May 2013 and started to receive TKM since July 2013 to decrease side effects of chemotherapy. From December 2013 to November 2014, she had received Herceptin 18 times more. The clinical outcomes were measured by computed tomography, laboratory findings including tumor markers (CEA, CA15-3), liver function test (AST, ALT), and numeric rating scales (NRS). Results : After 6 years of TKM treatment combined with standard chemotherapy, tumor size was partially decreased in lung, liver, right pleura and spleen. Levels of tumor markers also showed decrease. There were no severe adverse events induced by TKM based on National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE) version 4.0. Conclusion : This case suggests that TKM combined with standard chemotherapy could be a promising method for treating metastatic stage IV breast cancer.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.84-84
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• 2013

FcBP consisting of 13 amino acids specifically binds to Immunoglobulin G Fc domain. Initially, we utilized this peptide for preparation of antibody chip as a PEG composite for enhanced solubility. After then, the peptide conjugate was immobilized on agarose resin, resulting in highly efficient affinity column for antibody purification. The efficiency was comparable to commercial Protein A column. Recently, this peptide was conjugated with cell penetratingpeptide (CPP) on a backbone of GFP, affording antibody transducer, which carries antibody into live cells by simple mixing of antibody and the transducer in cell culture media. Antibody transduction into cells was monitored by live cell imaging. More recently, the FcBP was fused to ferritin cage, which consists of 24 ferritin protein molecules. The FcBP-ferritin cage showed greatly increased binding affinity to human IgG. Its binding was analyzed by QCM and SPR analysis. Finally, it was selectively delivered by Herceptin to SKBR3, a breast cancer cell, over MCF10A, non-tumorigenic cells.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1609-1615
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• 2016

Breast cancer is one of among all cancers with increased incidence, high mortality rate, and high economic and social costs. The the most common type of cancer among females worldwide, breast cancer is actually the uncontrolled proliferation of cells which attain malignancy. Recently it has shown that breast cancer contributes 11% among all types of cancer diagnosed globally on an annual basis and it is one of the leading causes of death among women. The human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine-protein kinase erbB-2 normally involved in the proliferation and division of breast cells. In some abnormal cases the HER2 gene does not work correctly and makes too many copies of itself. HER2-positive (HER2+) breast cancers constitute an aggressive type of breast cancer and tend to grow faster and are more likely to spread. However, therapies that specifically target HER2, such as Herceptin$^{(R)}$ (traztuzumab), are very effective. HER2 targeted therapies, has significantly improved the therapeutic outcome for patients with HER2 positive breast cancer.

• Proceedings of the Korean Vacuum Society Conference
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• 2013.02a
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• pp.110-111
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• 2013

FcBP consisting of 13 amino acids specifically binds to Immunoglobulin G Fc domain. Initially, we utilized this peptide for preparation of antibody chip as a PEG composite for enhanced solubility. After then, the peptide conjugate was immobilized on agarose resin, resulting in highly efficient affinity column for antibody purification. The efficiency was comparable to commercial Protein A column. Recently, this peptide was conjugated with cell penetrating peptide (CPP) on a backbone of GFP, affording antibody transducer, which carries antibody into live cells by simple mixing of antibody and the transducer in cell culture media. Antibody transduction into cells was monitored by live cell imaging. More recently, the FcBP was fused to ferritin cage, which consists of 24 ferritin protein molecules. The FcBP-ferritin cage showed greatly increased binding affinity to human IgG. Its binding was analyzed by QCM and SPR analysis. Finally, it was selectively delivered by Herceptin to SKBR3, a breast cancer cell, over MCF10A, non-tumorigenic cells (Fig. 1). Fig. 1. Fluorescent microscopic images of SKBR3 breast cancer cells (A~C) and MCF10A breast cells (D~F) treated with Cy3-trastuzumab/fFcBP-Pf_Fn complexes. Trastuzumab and FcBP-Pf_Fn, which were labeled with Cy3 (Cy3-trastuzumab) and fluorescein (fFcBP-Pf_Fn), respectively, selectively targeted SKBR3 over MCF10A.