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http://dx.doi.org/10.7314/APJCP.2012.13.6.2795

Anti-HER-2×anti-CD3 Bi-specific Antibodies Inhibit Growth of HCT-116 Colorectal Carcinoma Cells in Vitro and in Vivo  

Ren, Hui (Department of General Surgery, the Second Hospital, Jilin University)
Li, Jun (Department of Hematology and Oncology, China-Japan Union Hospital of Jilin University)
Liu, Jing-Jing (Department of General Surgery, the Second Hospital, Jilin University)
Guo, Hui-Ling (Department of General Surgery, the Second Hospital, Jilin University)
Jiang, Tao (Department of General Surgery, China-Japan Union Hospital of Jilin University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.13, no.6, 2012 , pp. 2795-2798 More about this Journal
Abstract
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.
Keywords
Anti-HER-2${\times}$anti-CD3 bispecific antibody; HER-2/neu; human colorectal carcinoma; nude mice;
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1 Albarello L, Pecciarini L, Doglioni C (2011). HER2 testing in gastric cancer. Adv Anat Pathol, 18, 53-9.   DOI
2 Argyriou AA, Kalofonos HP (2009). Recent advances relating to the clinical application of naked monoclonal antibodies in solid tumors. Mol Med, 15, 183-91.   DOI
3 Bang YJ, Van Cutsem E, Feyereislova A, et al (2010). Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet, 376, 687-97.   DOI
4 Baselga J, Norton L, Albanell J, Kim YM, Mendelsohn J (1999). Recombinant humanized anti-HER2 antibody (Herceptin) enhances the antitumor activity of paclitaxel and doxorubicin against HER2/neu overexpressing human breast cancer xenografts. Cancer Res, 58, 2825-31.
5 Chatenoud L (1993). CD3 antibody treatment stimulates the functional capability of regulatory T cells. Novartis Found Symp, 252:279-86; discussion 286-90.
6 Cuello M, Ettenberg SA, Clark AS, et al (2001). Down-regulation of the erbB-2 receptor by trastuzumab (herceptin) enhances tumor necrosis factor-related apoptosis-inducing ligandmediated apoptosis in breast and ovarian cancer cell lines that over-express erbB- 2. Cancer Res, 61, 4892-900.
7 Huang L, Chen S, Zha X, et al (2012). Expression feature of CD3, $Fc{\varepsilon}RI{\gamma}$, and Zap-70 in patients with chronic lymphocytic leukemia. Hematology, 17, 71-5.   DOI
8 Jemal A, Siegel R, Ward E, et al (2009). Cancer statistics, 2009. CA Cancer J Clin, 59, 225-49.   DOI   ScienceOn
9 Kiewe P, Hasmüller S, Kahlert S, et al (2006). Phase I trial of the trifunctional anti-HER2 x anti-CD3 antibody ertumaxomab in metastatic breast cancer. Clin Cancer Res, 12, 3085-91.   DOI
10 Liu HQ, Zhang SL, Song S (2012). HER-2/neu and TOPIIa expression in gastric cancer reflect disease severity. Hepatogastroenterology, 59, 1290-3.
11 Morishita A, Gong J, Nomura T, et al (2010). The use of protein array to identify targetable receptor tyrosine kinases for treatment of human colon cancer. Int J Oncol, 37, 829-35.
12 Nishio J, Feuerer M, Wong J, Mathis D, Benoist C (2010). Anti-CD3 therapy permits regulatory T cells to surmount T cell receptor-specified peripheral niche constraints. J Exp Med, 207, 1879-89.   DOI
13 Schroeder P, Lindemann C, Dettmar K, et al (2011). Trifunctional antibodies induce efficient antitumour activity with immune cells from head and neck squamous cell carcinoma patients after radio-chemotherapy treatment. Clin Transl Oncol, 13, 889-98.   DOI
14 Somlo G, Martel CL, Lau SK, et al (2012). A phase I/II prospective, single arm trial of gefitinib, trastuzumab, and docetaxel in patients with stage IV HER-2 positive metastatic breast cancer. Breast Cancer Res Treat, 131, 899-906. Epub 2011 Nov 1.   DOI
15 Xia L, Yuan YZ, Xu CD, et al (2002). Effects of epidermal growth factor on the growth of human colorectal cancer cell and the implanted tumor of nude mice. World J Gastroenterol, 8, 455-8.