Targeting non-human corona viruses to human cancer cells using a bispecific single-chain antibody
Identifieur interne : 001026 ( Main/Exploration ); précédent : 001025; suivant : 001027Targeting non-human corona viruses to human cancer cells using a bispecific single-chain antibody
Auteurs : T. Würdinger [Pays-Bas] ; M. H. Verheije [Pays-Bas] ; M. Raaben [Pays-Bas] ; B. J. Bosch [Pays-Bas] ; C. A. M. De Haan [Pays-Bas] ; V. W. Van Beusechem [Pays-Bas] ; P. J. M. Rottier [Pays-Bas] ; W. R. Gerritsen [Pays-Bas]Source :
- Gene therapy : (Basingstoke) [ 0969-7128 ] ; 2005.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein - responsible for receptor binding and subsequent cell entry through virus-cell membrane fusion - and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.
Affiliations:
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Würdinger</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M. H." last="Verheije">M. H. Verheije</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Raaben, M" sort="Raaben, M" uniqKey="Raaben M" first="M." last="Raaben">M. Raaben</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Bosch, B J" sort="Bosch, B J" uniqKey="Bosch B" first="B. J." last="Bosch">B. J. Bosch</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="De Haan, C A M" sort="De Haan, C A M" uniqKey="De Haan C" first="C. A. M." last="De Haan">C. A. M. De Haan</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Van Beusechem, V W" sort="Van Beusechem, V W" uniqKey="Van Beusechem V" first="V. W." last="Van Beusechem">V. W. Van Beusechem</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author><author><name sortKey="Rottier, P J M" sort="Rottier, P J M" uniqKey="Rottier P" first="P. J. M." last="Rottier">P. J. M. Rottier</name><affiliation wicri:level="4"><inist:fA14 i1="01"><s1>Virology Division, Department of Infectious Diseases and Immunology, Utrecht University</s1><s2>Utrecht</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Utrecht</settlement><region nuts="2" type="province">Utrecht (province)</region></placeName><orgName type="university">Université d'Utrecht</orgName></affiliation></author><author><name sortKey="Gerritsen, W R" sort="Gerritsen, W R" uniqKey="Gerritsen W" first="W. R." last="Gerritsen">W. R. Gerritsen</name><affiliation wicri:level="3"><inist:fA14 i1="02"><s1>Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center</s1><s2>Amsterdam</s2><s3>NLD</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>6 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>Pays-Bas</country><placeName><settlement type="city">Amsterdam</settlement><region nuts="2" type="province">Hollande-Septentrionale</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Gene therapy : (Basingstoke)</title><title level="j" type="abbreviated">Gene ther. : (Basingstoke)</title><idno type="ISSN">0969-7128</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Gene therapy : (Basingstoke)</title><title level="j" type="abbreviated">Gene ther. : (Basingstoke)</title><idno type="ISSN">0969-7128</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Bispecific antibody</term><term>Coronavirus</term><term>Epidermal growth factor receptor</term><term>Gene therapy</term><term>Human</term><term>Malignant tumor</term><term>Single chain antibody</term><term>Targeting</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Ciblage</term><term>Homme</term><term>Anticorps bispécifique</term><term>Anticorps simple chaîne</term><term>Thérapie génique</term><term>Tumeur maligne</term><term>Coronavirus</term><term>Récepteur EGFR</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">To explore the potential of using non-human coronaviruses for cancer therapy, we first established their ability to kill human tumor cells. We found that the feline infectious peritonitis virus (FIPV) and a felinized murine hepatitis virus (fMHV), both normally incapable of infecting human cells, could rapidly and effectively kill human cancer cells artificially expressing the feline coronavirus receptor aminopeptidase N. Also 3-D multilayer tumor spheroids established from such cells were effectively eradicated. Next, we investigated whether FIPV and fMHV could be targeted to human cancer cells by constructing a bispecific single-chain antibody directed on the one hand against the feline coronavirus spike protein - responsible for receptor binding and subsequent cell entry through virus-cell membrane fusion - and on the other hand against the human epidermal growth factor receptor (EGFR). The targeting antibody mediated specific infection of EGFR-expressing human cancer cells by both coronaviruses. Furthermore, in the presence of the targeting antibody, infected cancer cells formed syncytia typical of productive coronavirus infection. By their potent cytotoxicity, the selective targeting of non-human coronaviruses to human cancer cells provides a rationale for further investigations into the use of these viruses as anticancer agents.</div></front></TEI><affiliations><list><country><li>Pays-Bas</li></country><region><li>Hollande-Septentrionale</li><li>Utrecht (province)</li></region><settlement><li>Amsterdam</li><li>Utrecht</li></settlement><orgName><li>Université d'Utrecht</li></orgName></list><tree><country name="Pays-Bas"><region name="Utrecht (province)"><name sortKey="Wurdinger, T" sort="Wurdinger, T" uniqKey="Wurdinger T" first="T." last="Würdinger">T. Würdinger</name></region><name sortKey="Bosch, B J" sort="Bosch, B J" uniqKey="Bosch B" first="B. J." last="Bosch">B. J. Bosch</name><name sortKey="De Haan, C A M" sort="De Haan, C A M" uniqKey="De Haan C" first="C. A. M." last="De Haan">C. A. M. De Haan</name><name sortKey="Gerritsen, W R" sort="Gerritsen, W R" uniqKey="Gerritsen W" first="W. R." last="Gerritsen">W. R. Gerritsen</name><name sortKey="Raaben, M" sort="Raaben, M" uniqKey="Raaben M" first="M." last="Raaben">M. Raaben</name><name sortKey="Rottier, P J M" sort="Rottier, P J M" uniqKey="Rottier P" first="P. J. M." last="Rottier">P. J. M. Rottier</name><name sortKey="Van Beusechem, V W" sort="Van Beusechem, V W" uniqKey="Van Beusechem V" first="V. W." last="Van Beusechem">V. W. Van Beusechem</name><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M. H." last="Verheije">M. H. Verheije</name><name sortKey="Verheije, M H" sort="Verheije, M H" uniqKey="Verheije M" first="M. H." last="Verheije">M. H. Verheije</name><name sortKey="Wurdinger, T" sort="Wurdinger, T" uniqKey="Wurdinger T" first="T." last="Würdinger">T. Würdinger</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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