Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo
The epidermal growth factor receptor (EGFR) is an attractive target for the immunotherapy of EGFR+ tumors. Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific a...
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| Veröffentlicht in: | Oncology reports 2015-11, Vol.34 (5), p.2567-2575 |
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| creator | MA, PAN HE, QIANG LI, WEI LI, XIANLIANG HAN, HUAMIN JIN, MENGMENG LIU, CHANGZHEN TAO, HUA MA, JUAN GAO, BIN |
| description | The epidermal growth factor receptor (EGFR) is an attractive target for the immunotherapy of EGFR+ tumors. Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for its ability to redirect CIK cells to target EGFR-positive glioblastoma. The specific cytolytic activity of CIK cells armed with EGFRBi-Ab against U87MG-luc cells was evaluated by bioluminescent signal generated using luciferase reporter assay which did not alter the surface molecule expression or proliferation ability of U87MG cells. In contrast to unarmed CIK cells, increased cytotoxic activity of EGFRBi-armed CIK cells against the U87MG-luc target was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, EGFRBi-armed CIK cells secreted significantly higher levels of IFN-γ, TNF-α, and IL-2 than their unarmed CIK counterpart cells. Furthermore, in glioblastoma xenograft mice, infusion of the EGFRBi-armed CIK cells successfully inhibited the growth of glioblastoma tumors. The in vitro and in vivo antitumor effects of EGFRBi-armed CIK cells support their clinical use for treatment of glioblastoma in the future. |
| doi_str_mv | 10.3892/or.2015.4233 |
| format | Article |
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Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for its ability to redirect CIK cells to target EGFR-positive glioblastoma. The specific cytolytic activity of CIK cells armed with EGFRBi-Ab against U87MG-luc cells was evaluated by bioluminescent signal generated using luciferase reporter assay which did not alter the surface molecule expression or proliferation ability of U87MG cells. In contrast to unarmed CIK cells, increased cytotoxic activity of EGFRBi-armed CIK cells against the U87MG-luc target was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, EGFRBi-armed CIK cells secreted significantly higher levels of IFN-γ, TNF-α, and IL-2 than their unarmed CIK counterpart cells. Furthermore, in glioblastoma xenograft mice, infusion of the EGFRBi-armed CIK cells successfully inhibited the growth of glioblastoma tumors. The in vitro and in vivo antitumor effects of EGFRBi-armed CIK cells support their clinical use for treatment of glioblastoma in the future.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2015.4233</identifier><identifier>PMID: 26323605</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Animals ; Antibodies, Bispecific - administration & dosage ; Antibodies, Bispecific - pharmacology ; Antigens ; bispecific antibody ; Brain cancer ; Cancer therapies ; CD3 Complex - immunology ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Cell Survival - drug effects ; Chemotherapy ; Clinical trials ; Cytokine-Induced Killer Cells - immunology ; Cytokine-Induced Killer Cells - transplantation ; Cytokines ; Development and progression ; Efficiency ; EGFR ; Enzymes ; Genetic aspects ; glioblastoma ; Glioblastoma - immunology ; Glioblastoma - metabolism ; Glioblastoma - therapy ; Glioblastoma multiforme ; Growth factors ; Health aspects ; Humans ; Immune response ; Immunoglobulins ; Immunotherapy ; Immunotherapy - methods ; In Vitro Techniques ; Killer cells ; Laboratories ; Life sciences ; luciferase ; Lymphocytes ; Medical prognosis ; Mice ; Plasmids ; Receptor, Epidermal Growth Factor - immunology ; Regulation ; Rodents ; Tumors ; Xenograft Model Antitumor Assays</subject><ispartof>Oncology reports, 2015-11, Vol.34 (5), p.2567-2575</ispartof><rights>Copyright: © Ma</rights><rights>COPYRIGHT 2015 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-7e649c0df1ea0f2ad94cb35c8d5a0e37994183e92527a4807b994342dad255fb3</citedby><cites>FETCH-LOGICAL-c486t-7e649c0df1ea0f2ad94cb35c8d5a0e37994183e92527a4807b994342dad255fb3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26323605$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MA, PAN</creatorcontrib><creatorcontrib>HE, QIANG</creatorcontrib><creatorcontrib>LI, WEI</creatorcontrib><creatorcontrib>LI, XIANLIANG</creatorcontrib><creatorcontrib>HAN, HUAMIN</creatorcontrib><creatorcontrib>JIN, MENGMENG</creatorcontrib><creatorcontrib>LIU, CHANGZHEN</creatorcontrib><creatorcontrib>TAO, HUA</creatorcontrib><creatorcontrib>MA, JUAN</creatorcontrib><creatorcontrib>GAO, BIN</creatorcontrib><title>Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo</title><title>Oncology reports</title><addtitle>Oncol Rep</addtitle><description>The epidermal growth factor receptor (EGFR) is an attractive target for the immunotherapy of EGFR+ tumors. Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for its ability to redirect CIK cells to target EGFR-positive glioblastoma. The specific cytolytic activity of CIK cells armed with EGFRBi-Ab against U87MG-luc cells was evaluated by bioluminescent signal generated using luciferase reporter assay which did not alter the surface molecule expression or proliferation ability of U87MG cells. In contrast to unarmed CIK cells, increased cytotoxic activity of EGFRBi-armed CIK cells against the U87MG-luc target was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, EGFRBi-armed CIK cells secreted significantly higher levels of IFN-γ, TNF-α, and IL-2 than their unarmed CIK counterpart cells. Furthermore, in glioblastoma xenograft mice, infusion of the EGFRBi-armed CIK cells successfully inhibited the growth of glioblastoma tumors. The in vitro and in vivo antitumor effects of EGFRBi-armed CIK cells support their clinical use for treatment of glioblastoma in the future.</description><subject>Animals</subject><subject>Antibodies, Bispecific - administration & dosage</subject><subject>Antibodies, Bispecific - pharmacology</subject><subject>Antigens</subject><subject>bispecific antibody</subject><subject>Brain cancer</subject><subject>Cancer therapies</subject><subject>CD3 Complex - immunology</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Cell Survival - drug effects</subject><subject>Chemotherapy</subject><subject>Clinical trials</subject><subject>Cytokine-Induced Killer Cells - immunology</subject><subject>Cytokine-Induced Killer Cells - transplantation</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Efficiency</subject><subject>EGFR</subject><subject>Enzymes</subject><subject>Genetic aspects</subject><subject>glioblastoma</subject><subject>Glioblastoma - immunology</subject><subject>Glioblastoma - metabolism</subject><subject>Glioblastoma - therapy</subject><subject>Glioblastoma multiforme</subject><subject>Growth factors</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Immune response</subject><subject>Immunoglobulins</subject><subject>Immunotherapy</subject><subject>Immunotherapy - methods</subject><subject>In Vitro Techniques</subject><subject>Killer cells</subject><subject>Laboratories</subject><subject>Life sciences</subject><subject>luciferase</subject><subject>Lymphocytes</subject><subject>Medical prognosis</subject><subject>Mice</subject><subject>Plasmids</subject><subject>Receptor, Epidermal Growth Factor - immunology</subject><subject>Regulation</subject><subject>Rodents</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1021-335X</issn><issn>1791-2431</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNptks9rFTEQxxdRbK3ePEtAKD2YZ37ubo6PZ1uFgiAK3kI2mW3TZjfPJFt8_313ebW1IjkkM_nMNxPmW1VvKVnxVrGPMa0YoXIlGOfPqkPaKIqZ4PT5fCaMYs7lz4PqVc7XhLCG1OpldcBqznhN5GG1XY_F480njn6j0_Ozb6jzeQvW994iM1910e1QAucT2JKR3ZV440fAfnSTBYdufAiQkIUQMioRXQYfu2ByiYNBfkS3vqQ4K7l9cBtfVy96EzK8ud-Pqh9np983n_HF1_Mvm_UFtqKtC26gFsoS11MwpGfGKWE7Lm3rpCHAG6UEbTkoJlljREuabs5wwZxxTMq-40fVyV53m-KvCXLRg89Lm2aEOGVNG9oqojhpZ_T9P-h1nNI4d6ep4pzWirXqkbo0AbQf-1iSsYuoXgsh26ZmaqFW_6Hm5WDwNo7Q-zn_pOD4r4IrMKFc5Rim4uOYn4If9qBNMecEvd4mP5i005ToxQk6Jr04QS9OmPF395-augHcA_xn9I8P5-08Hu9ifmBiwlxgIjGTdcPvAA2st_U</recordid><startdate>20151101</startdate><enddate>20151101</enddate><creator>MA, PAN</creator><creator>HE, QIANG</creator><creator>LI, WEI</creator><creator>LI, XIANLIANG</creator><creator>HAN, HUAMIN</creator><creator>JIN, MENGMENG</creator><creator>LIU, CHANGZHEN</creator><creator>TAO, HUA</creator><creator>MA, JUAN</creator><creator>GAO, BIN</creator><general>D.A. 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Adjuvant immunotherapy with cytokine-induced killer (CIK) cells may improve progression-free survival rates in patients suffering from cancer. In the present study, we examined the bispecific antibody anti-CD3 x anti-EGFR (EGFRBi-Ab) for its ability to redirect CIK cells to target EGFR-positive glioblastoma. The specific cytolytic activity of CIK cells armed with EGFRBi-Ab against U87MG-luc cells was evaluated by bioluminescent signal generated using luciferase reporter assay which did not alter the surface molecule expression or proliferation ability of U87MG cells. In contrast to unarmed CIK cells, increased cytotoxic activity of EGFRBi-armed CIK cells against the U87MG-luc target was observed at effector/target (E/T) ratios of 5:1, 10:1, and 20:1. Moreover, EGFRBi-armed CIK cells secreted significantly higher levels of IFN-γ, TNF-α, and IL-2 than their unarmed CIK counterpart cells. Furthermore, in glioblastoma xenograft mice, infusion of the EGFRBi-armed CIK cells successfully inhibited the growth of glioblastoma tumors. The in vitro and in vivo antitumor effects of EGFRBi-armed CIK cells support their clinical use for treatment of glioblastoma in the future.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>26323605</pmid><doi>10.3892/or.2015.4233</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Antibodies, Bispecific - administration & dosage Antibodies, Bispecific - pharmacology Antigens bispecific antibody Brain cancer Cancer therapies CD3 Complex - immunology Cell Line, Tumor Cell Proliferation - drug effects Cell Survival - drug effects Chemotherapy Clinical trials Cytokine-Induced Killer Cells - immunology Cytokine-Induced Killer Cells - transplantation Cytokines Development and progression Efficiency EGFR Enzymes Genetic aspects glioblastoma Glioblastoma - immunology Glioblastoma - metabolism Glioblastoma - therapy Glioblastoma multiforme Growth factors Health aspects Humans Immune response Immunoglobulins Immunotherapy Immunotherapy - methods In Vitro Techniques Killer cells Laboratories Life sciences luciferase Lymphocytes Medical prognosis Mice Plasmids Receptor, Epidermal Growth Factor - immunology Regulation Rodents Tumors Xenograft Model Antitumor Assays |
| title | Anti-CD3 x EGFR bispecific antibody redirects cytokine-induced killer cells to glioblastoma in vitro and in vivo |
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