HER2 as a promising target for cytotoxicity T cells in human melanoma therapy
Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a tar...
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| Veröffentlicht in: | PloS one 2013-08, Vol.8 (8), p.e73261 |
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| creator | Ma, Juan Han, Huamin Liu, Deruo Li, Wei Feng, Hongxiang Xue, Xin Wu, Xiaoran Niu, Ge Zhang, Ge Zhao, Yunfeng Liu, Changzhen Tao, Hua Gao, Bin |
| description | Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future. |
| doi_str_mv | 10.1371/journal.pone.0073261 |
| format | Article |
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Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0073261</identifier><identifier>PMID: 24015299</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Animals ; Antibodies, Bispecific - immunology ; Antibodies, Bispecific - pharmacology ; Antibodies, Neoplasm - immunology ; Antibodies, Neoplasm - pharmacology ; Anticancer properties ; Biophysics ; Bispecific antibodies ; Breast cancer ; Cancer therapies ; CD3 antigen ; CD3 Complex - immunology ; CD3 Complex - metabolism ; CD69 antigen ; Cell culture ; Cell proliferation ; Cytolytic activity ; Cytotoxicity ; Effector cells ; ErbB-2 protein ; Gene Expression Regulation, Enzymologic - drug effects ; Gene Expression Regulation, Enzymologic - immunology ; Gene Expression Regulation, Neoplastic - drug effects ; Gene Expression Regulation, Neoplastic - immunology ; Growth factors ; Humans ; Immunology ; Immunotherapy ; Interferon ; K562 Cells ; Kinases ; Laboratories ; Lymphocyte Activation - drug effects ; Lymphocyte Activation - immunology ; Lymphocytes ; Lymphocytes T ; Melanoma ; Melanoma - drug therapy ; Melanoma - immunology ; Melanoma - pathology ; Metastasis ; Mice ; Mice, SCID ; Monoclonal antibodies ; Receptor, ErbB-2 - genetics ; Receptor, ErbB-2 - immunology ; Receptor, ErbB-2 - metabolism ; Surgery ; T-Lymphocytes - immunology ; T-Lymphocytes - pathology ; Therapy ; Thoracic surgery ; Toxicity ; Tumor cells ; Tumors ; Xenograft Model Antitumor Assays ; Xenografts ; γ-Interferon</subject><ispartof>PloS one, 2013-08, Vol.8 (8), p.e73261</ispartof><rights>2013 Ma et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2013 Ma et al 2013 Ma et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c526t-e8ffe0a981fbb3390d6f5df779dec19067503eb3aaad86d78cf6638c22331b6a3</citedby><cites>FETCH-LOGICAL-c526t-e8ffe0a981fbb3390d6f5df779dec19067503eb3aaad86d78cf6638c22331b6a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754977/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754977/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24015299$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ma, Juan</creatorcontrib><creatorcontrib>Han, Huamin</creatorcontrib><creatorcontrib>Liu, Deruo</creatorcontrib><creatorcontrib>Li, Wei</creatorcontrib><creatorcontrib>Feng, Hongxiang</creatorcontrib><creatorcontrib>Xue, Xin</creatorcontrib><creatorcontrib>Wu, Xiaoran</creatorcontrib><creatorcontrib>Niu, Ge</creatorcontrib><creatorcontrib>Zhang, Ge</creatorcontrib><creatorcontrib>Zhao, Yunfeng</creatorcontrib><creatorcontrib>Liu, Changzhen</creatorcontrib><creatorcontrib>Tao, Hua</creatorcontrib><creatorcontrib>Gao, Bin</creatorcontrib><title>HER2 as a promising target for cytotoxicity T cells in human melanoma therapy</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Anti-HER2/neu antibody therapy has been reported to mediate tumor regression of HER2/ neu(+) tumors. Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. 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Here we demonstrated the expression of HER2 in a wide range of human melanoma cells including a primary culture and seven cell lines, and we further investigated whether HER2 could be served as a target for T cell mediated immunotherapy of human melanoma. Specific cytolytic activity of activated T cells (ATC) armed with anti-CD3 x anti-HER2 bispecific antibody (HER2Bi-Ab) against Malme-3M-luc cells was evaluated by bioluminescent signal generated by luciferase reporter which did not alter HER2 expression or proliferation ability of Malme-3M cells. Contrast with unarmed ATC, increased cytotoxic activity of HER2Bi-armed ATC against Malme-3M-luc cells was observed at effector/target (E/T) ratios of 1:1, 5:1, and 20:1. Moreover, HER2Bi-armed ATC expressed higher level of activation marker CD69 and secreted significantly higher level of IFN-γ than unarmed ATC counterpart at the E/T ratio of 20:1. In addition, compared with anti-HER2 mAb (Herceptin®) or unarmed ATC, HER2Bi-armed ATC showed remarkable suppression effect on Malme-3M-luc tumor cells. Furthermore, in melanoma tumor cell xenograft mice, infusion of HER2Bi-armed ATC successfully inhibited the growth of melanoma tumors. The anti-tumor effect of HER2Bi-armed ATC may provide a promising immunotherapy for melanoma in the future.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>24015299</pmid><doi>10.1371/journal.pone.0073261</doi><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1428305645 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Animals Antibodies, Bispecific - immunology Antibodies, Bispecific - pharmacology Antibodies, Neoplasm - immunology Antibodies, Neoplasm - pharmacology Anticancer properties Biophysics Bispecific antibodies Breast cancer Cancer therapies CD3 antigen CD3 Complex - immunology CD3 Complex - metabolism CD69 antigen Cell culture Cell proliferation Cytolytic activity Cytotoxicity Effector cells ErbB-2 protein Gene Expression Regulation, Enzymologic - drug effects Gene Expression Regulation, Enzymologic - immunology Gene Expression Regulation, Neoplastic - drug effects Gene Expression Regulation, Neoplastic - immunology Growth factors Humans Immunology Immunotherapy Interferon K562 Cells Kinases Laboratories Lymphocyte Activation - drug effects Lymphocyte Activation - immunology Lymphocytes Lymphocytes T Melanoma Melanoma - drug therapy Melanoma - immunology Melanoma - pathology Metastasis Mice Mice, SCID Monoclonal antibodies Receptor, ErbB-2 - genetics Receptor, ErbB-2 - immunology Receptor, ErbB-2 - metabolism Surgery T-Lymphocytes - immunology T-Lymphocytes - pathology Therapy Thoracic surgery Toxicity Tumor cells Tumors Xenograft Model Antitumor Assays Xenografts γ-Interferon |
| title | HER2 as a promising target for cytotoxicity T cells in human melanoma therapy |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T09%3A55%3A34IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=HER2%20as%20a%20promising%20target%20for%20cytotoxicity%20T%20cells%20in%20human%20melanoma%20therapy&rft.jtitle=PloS%20one&rft.au=Ma,%20Juan&rft.date=2013-08-27&rft.volume=8&rft.issue=8&rft.spage=e73261&rft.pages=e73261-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0073261&rft_dat=%3Cproquest_plos_%3E3056472901%3C/proquest_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1428305645&rft_id=info:pmid/24015299&rft_doaj_id=oai_doaj_org_article_ac5577cb7b434a41985899dbb32e998d&rfr_iscdi=true |