H2Mab‑19, an anti‑human epidermal growth factor receptor 2 monoclonal antibody exerts antitumor activity in mouse oral cancer xenografts

Takei,Junko; Kaneko,Mika Kato; Ohishi,Tomokazu; Kawada,Manabu; Harada,Hiroyuki; Kato,Yukinari

doi:10.3892/etm.2020.8765

H2Mab‑19, an anti‑human epidermal growth factor receptor 2 monoclonal antibody exerts antitumor activity in mouse oral cancer xenografts

Authors:
- Junko Takei
- Mika Kato Kaneko
- Tomokazu Ohishi
- Manabu Kawada
- Hiroyuki Harada
- Yukinari Kato
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Affiliations: Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980‑8575, Japan, Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Numazu‑shi, Shizuoka 410‑0301, Japan, Department of Oral and Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113‑8510, Japan
Published online on: May 18, 2020 https://doi.org/10.3892/etm.2020.8765
Pages: 846-853
Copyright : © Takei et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Human epidermal growth factor receptor 2 (HER2) is reported to be overexpressed in breast cancers and is associated with poor clinical outcome. Trastuzumab is a humanized anti‑HER2 antibody that offers significant survival benefits to patients with HER2‑overexpressing breast cancer. In this study, a novel anti‑HER2 monoclonal antibody (mAb), H2Mab‑19 (IgG2b, kappa) was developed. Antibody‑dependent cellular cytotoxicity (ADCC), complement‑dependent cytotoxicity (CDC), and antitumor activity of H2Mab‑19 were investigated using both breast cancer and oral cancer cell lines. H2Mab‑19 demonstrated cytotoxicity in BT‑474 (a human breast cancer cell line) and HSC‑2 or SAS (human oral cancer cell lines). H2Mab‑19 also possessed both ADCC and CDC activity against BT‑474, HSC‑2, and SAS cell lines. In comparison to control mouse IgG, H2Mab‑19 significantly reduced tumor development in BT‑474, HSC‑2, and SAS xenografts. Collectively, these results suggest that treatment with H2Mab‑19 may be a useful therapy for patients with HER2‑expressing breast and oral cancers.

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1	Howlader N, Altekruse SF, Li CI, Chen VW, Clarke CA, Ries LA and Cronin KA: US incidence of breast cancer subtypes defined by joint hormone receptor and HER2 status. J Natl Cancer Inst. 106(dju055)2014.PubMed/NCBI View Article : Google Scholar
2	Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL: Human breast cancer: Correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 235:177–182. 1987.PubMed/NCBI View Article : Google Scholar
3	Xie S, Zhang H, Wang X, Ge Q and Hu J: The relative efficacy and safety of targeted agents used in combination with chemotherapy in treating patients with untreated advanced gastric cancer: A network meta-analysis. Oncotarget. 8:26959–26968. 2017.PubMed/NCBI View Article : Google Scholar
4	Harder J, Ihorst G, Heinemann V, Hofheinz R, Moehler M, Buechler P, Kloeppel G, Röcken C, Bitzer M, Boeck S, et al: Multicentre phase II trial of trastuzumab and capecitabine in patients with HER2 overexpressing metastatic pancreatic cancer. Br J Cancer. 106:1033–1038. 2012.PubMed/NCBI View Article : Google Scholar
5	Kim EK, Kim KA, Lee CY and Shim HS: The frequency and clinical impact of HER2 alterations in lung adenocarcinoma. PLoS One. 12(e0171280)2017.PubMed/NCBI View Article : Google Scholar
6	Seo AN, Kwak Y, Kim DW, Kang SB, Choe G, Kim WH and Lee HS: HER2 status in colorectal cancer: Its clinical significance and the relationship between HER2 gene amplification and expression. PLoS One. 9(e98528)2014.PubMed/NCBI View Article : Google Scholar
7	Lambert JM and Chari RV: Ado-trastuzumab emtansine (T-DM1): An antibody-drug conjugate (ADC) for HER2-positive breast cancer. J Med Chem. 57:6949–6964. 2014.PubMed/NCBI View Article : Google Scholar
8	Valabrega G, Montemurro F and Aglietta M: Trastuzumab: Mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer. Ann Oncol. 18:977–984. 2007.PubMed/NCBI View Article : Google Scholar
9	Amiri-Kordestani L, Wedam S, Zhang L, Tang S, Tilley A, Ibrahim A, Justice R, Pazdur R and Cortazar P: First FDA approval of neoadjuvant therapy for breast cancer: Pertuzumab for the treatment of patients with HER2-positive breast cancer. Clin Cancer Res. 20:5359–5364. 2014.PubMed/NCBI View Article : Google Scholar
10	Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, Fleming T, Eiermann W, Wolter J, Pegram M, et al: Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 344:783–792. 2001.PubMed/NCBI View Article : Google Scholar
11	Swain SM, Kim SB, Cortés J, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Knott A, et al: Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): Overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 14:461–471. 2013.PubMed/NCBI View Article : Google Scholar
12	Doi T, Shitara K, Naito Y, Shimomura A, Fujiwara Y, Yonemori K, Shimizu C, Shimoi T, Kuboki Y, Matsubara N, et al: Safety, pharmacokinetics, and antitumour activity of trastuzumab deruxtecan (DS-8201), a HER2-targeting antibody-drug conjugate, in patients with advanced breast and gastric or gastro-oesophageal tumours: A phase 1 dose-escalation study. Lancet Oncol. 18:1512–1522. 2017.PubMed/NCBI View Article : Google Scholar
13	Nakada T, Sugihara K, Jikoh T, Abe Y and Agatsuma T: The latest research and development into the antibody-drug conjugate, [fam-] trastuzumab deruxtecan (DS-8201a), for HER2 cancer therapy. Chem Pharm Bull (Tokyo). 67:173–185. 2019.PubMed/NCBI View Article : Google Scholar
14	Itai S, Fujii Y, Kaneko MK, Yamada S, Nakamura T, Yanaka M, Saidoh N, Chang YW, Handa S, Takahashi M, et al: H2Mab-77 is a sensitive and specific anti-HER2 monoclonal antibody against breast cancer. Monoclon Antib Immunodiagn Immunother. 36:143–148. 2017.PubMed/NCBI View Article : Google Scholar
15	Kato Y, Kunita A, Abe S, Ogasawara S, Fujii Y, Oki H, Fukayama M, Nishioka Y and Kaneko MK: The chimeric antibody chLpMab-7 targeting human podoplanin suppresses pulmonary metastasis via ADCC and CDC rather than via its neutralizing activity. Oncotarget. 6:36003–36018. 2015.PubMed/NCBI View Article : Google Scholar
16	Kaneko MK, Yamada S, Itai S and Kato Y: Development of an anti-HER2 monoclonal antibody H2Mab-139 against colon cancer. Monoclon Antib Immunodiagn Immunother. 37:59–62. 2018.PubMed/NCBI View Article : Google Scholar
17	Fujii Y, Kaneko MK and Kato Y: MAP tag: A novel tagging system for protein purification and detection. Monoclon Antib Immunodiagn Immunother. 35:293–299. 2016.PubMed/NCBI View Article : Google Scholar
18	Al-Saden N, Lam K, Chan C and Reilly RM: Positron-emission tomography of HER2-positive breast cancer xenografts in mice with ⁸⁹Zr-labeled trastuzumab-DM1: A comparison with ⁸⁹Zr-labeled trastuzumab. Mol Pharm. 15:3383–3393. 2018.PubMed/NCBI View Article : Google Scholar
19	Kato Y and Kaneko MK: A cancer-specific monoclonal antibody recognizes the aberrantly glycosylated podoplanin. Sci Rep. 4(5924)2014.PubMed/NCBI View Article : Google Scholar
20	Yamada S, Itai S, Nakamura T, Chang YW, Harada H, Suzuki H, Kaneko MK and Kato Y: Establishment of H₂Mab-119, an anti-human epidermal growth factor receptor 2 monoclonal antibody, against pancreatic cancer. Monoclon Antib Immunodiagn Immunother. 36:287–290. 2017.PubMed/NCBI View Article : Google Scholar
21	Kaneko MK, Nakamura T, Honma R, Ogasawara S, Fujii Y, Abe S, Takagi M, Harada H, Suzuki H, Nishioka Y and Kato Y: Development and characterization of anti-glycopeptide monoclonal antibodies against human podoplanin, using glycan-deficient cell lines generated by CRISPR/Cas9 and TALEN. Cancer Med. 6:382–396. 2017.PubMed/NCBI View Article : Google Scholar
22	Ogasawara S, Kaneko MK and Kato Y: LpMab-19 recognizes sialylated O-Glycan on Thr76 of human podoplanin. Monoclon Antib Immunodiagn Immunother. 35:245–253. 2016.PubMed/NCBI View Article : Google Scholar
23	Fiedler W, Stoeger H, Perotti A, Gastl G, Weidmann J, Dietrich B, Baumeister H, Danielczyk A, Goletz S, Salzberg M and De Dosso S: Phase I study of TrasGEX, a glyco-optimised anti-HER2 monoclonal antibody, in patients with HER2-positive solid tumours. ESMO Open. 3(e000381)2018.PubMed/NCBI View Article : Google Scholar
24	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar
25	Hashibe M, Brennan P, Chuang SC, Boccia S, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, et al: Interaction between tobacco and alcohol use and the risk of head and neck cancer: Pooled analysis in the international head and neck cancer epidemiology consortium. Cancer Epidemiol Biomarkers Prev. 18:541–550. 2009.PubMed/NCBI View Article : Google Scholar
26	Tota JE, Anderson WF, Coffey C, Califano J, Cozen W, Ferris RL, St John M, Cohen EEW and Chaturvedi AK: Rising incidence of oral tongue cancer among white men and women in the United States, 1973-2012. Oral Oncol. 67:146–152. 2017.PubMed/NCBI View Article : Google Scholar
27	Hussein AA, Helder MN, de Visscher JG, Leemans CR, Braakhuis BJ, de Vet HCW and Forouzanfar T: Global incidence of oral and oropharynx cancer in patients younger than 45 years versus older patients: A systematic review. Eur J Cancer. 82:115–127. 2017.PubMed/NCBI View Article : Google Scholar
28	Bagan J, Sarrion G and Jimenez Y: Oral cancer: Clinical features. Oral Oncol. 46:414–417. 2010.PubMed/NCBI View Article : Google Scholar
29	Rivera C: Essentials of oral cancer. Int J Clin Exp Pathol. 8:11884–11894. 2015.PubMed/NCBI
30	Guneri P and Epstein JB: Late stage diagnosis of oral cancer: Components and possible solutions. Oral Oncol. 50:1131–1136. 2014.PubMed/NCBI View Article : Google Scholar
31	Vokes EE: Induction chemotherapy for head and neck cancer: Recent data. Oncologist. 15 (Suppl 3)(S3-S7)2010.PubMed/NCBI View Article : Google Scholar
32	Marcazzan S, Varoni EM, Blanco E, Lodi G and Ferrari M: Nanomedicine, an emerging therapeutic strategy for oral cancer therapy. Oral Oncol. 76:1–7. 2018.PubMed/NCBI View Article : Google Scholar
33	Furness S, Glenny AM, Worthington HV, Pavitt S, Oliver R, Clarkson JE, Macluskey M, Chan KK and Conway DI: Interventions for the treatment of oral cavity and oropharyngeal cancer: Chemotherapy. Cochrane Database Syst Rev. CD006386:2011.PubMed/NCBI View Article : Google Scholar
34	Bonner JA, Harari PM, Giralt J, Azarnia N, Shin DM, Cohen RB, Jones CU, Sur R, Raben D, Jassem J, et al: Radiotherapy plus cetuximab for squamous-cell carcinoma of the head and neck. N Engl J Med. 354:567–578. 2006.PubMed/NCBI View Article : Google Scholar
35	Vermorken JB, Mesia R, Rivera F, Remenar E, Kawecki A, Rottey S, Erfan J, Zabolotnyy D, Kienzer HR, Cupissol D, et al: Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 359:1116–1127. 2008.PubMed/NCBI View Article : Google Scholar
36	Naruse T, Yanamoto S, Matsushita Y, Sakamoto Y, Morishita K, Ohba S, Shiraishi T, Yamada SI, Asahina I and Umeda M: Cetuximab for the treatment of locally advanced and recurrent/metastatic oral cancer: An investigation of distant metastasis. Mol Clin Oncol. 5:246–252. 2016.PubMed/NCBI View Article : Google Scholar
37	Amit M, Yen TC, Liao CT, Chaturvedi P, Agarwal JP, Kowalski LP, Ebrahimi A, Clark JR, Kreppel M, Zöller J, et al: Improvement in survival of patients with oral cavity squamous cell carcinoma: An international collaborative study. Cancer. 119:4242–4248. 2013.PubMed/NCBI View Article : Google Scholar
38	Hanken H, Gaudin R, Gröbe A, Fraederich M, Eichhorn W, Smeets R, Simon R, Sauter G, Grupp K, Izbicki JR, et al: Her2 expression and gene amplification is rarely detectable in patients with oral squamous cell carcinomas. J Oral Pathol Med. 43:304–308. 2014.PubMed/NCBI View Article : Google Scholar
39	Yan M, Schwaederle M, Arguello D, Millis SZ, Gatalica Z and Kurzrock R: HER2 expression status in diverse cancers: Review of results from 37,992 patients. Cancer Metastasis Rev. 34:157–164. 2015.PubMed/NCBI View Article : Google Scholar
40	Kondo N, Ishiguro Y, Kimura M, Sano D, Fujita K, Sakakibara A, Taguchi T, Toth G, Matsuda H and Tsukuda M: Antitumor effect of gefitinib on head and neck squamous cell carcinoma enhanced by trastuzumab. Oncol Rep. 20:373–378. 2008.PubMed/NCBI
41	Kondo N, Tsukuda M, Sakakibara A, Takahashi H, Hyakusoku H, Komatsu M, Niho T, Nakazaki K and Toth G: Combined molecular targeted drug therapy for EGFR and HER-2 in head and neck squamous cell carcinoma cell lines. Int J Oncol. 40:1805–1812. 2012.PubMed/NCBI View Article : Google Scholar