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Targeting non-human corona viruses to human cancer cells using a bispecific single-chain antibody

Identifieur interne : 000013 ( PascalFrancis/Curation ); précédent : 000012; suivant : 000014

Targeting 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 :

RBID : Pascal:05-0422331

Descripteurs français

English descriptors

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.
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Pascal:05-0422331

Le document en format XML

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<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>
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<s1>VAN BEUSECHEM (V. W.)</s1>
</fA11>
<fA11 i1="07" i2="1">
<s1>ROTTIER (P. J. M.)</s1>
</fA11>
<fA11 i1="08" i2="1">
<s1>GERRITSEN (W. R.)</s1>
</fA11>
<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>
</fA14>
<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>
</fA14>
<fA20>
<s1>1394-1404</s1>
</fA20>
<fA21>
<s1>2005</s1>
</fA21>
<fA23 i1="01">
<s0>ENG</s0>
</fA23>
<fA43 i1="01">
<s1>INIST</s1>
<s2>26274</s2>
<s5>354000131717160060</s5>
</fA43>
<fA44>
<s0>0000</s0>
<s1>© 2005 INIST-CNRS. All rights reserved.</s1>
</fA44>
<fA45>
<s0>42 ref.</s0>
</fA45>
<fA47 i1="01" i2="1">
<s0>05-0422331</s0>
</fA47>
<fA60>
<s1>P</s1>
</fA60>
<fA61>
<s0>A</s0>
</fA61>
<fA64 i1="01" i2="1">
<s0>Gene therapy : (Basingstoke)</s0>
</fA64>
<fA66 i1="01">
<s0>GBR</s0>
</fA66>
<fC01 i1="01" l="ENG">
<s0>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.</s0>
</fC01>
<fC02 i1="01" i2="X">
<s0>002A31D01D</s0>
</fC02>
<fC02 i1="02" i2="X">
<s0>002B27D03</s0>
</fC02>
<fC02 i1="03" i2="X">
<s0>215</s0>
</fC02>
<fC03 i1="01" i2="X" l="FRE">
<s0>Ciblage</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="ENG">
<s0>Targeting</s0>
<s5>01</s5>
</fC03>
<fC03 i1="01" i2="X" l="SPA">
<s0>Blancado</s0>
<s5>01</s5>
</fC03>
<fC03 i1="02" i2="X" l="FRE">
<s0>Homme</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="ENG">
<s0>Human</s0>
<s5>02</s5>
</fC03>
<fC03 i1="02" i2="X" l="SPA">
<s0>Hombre</s0>
<s5>02</s5>
</fC03>
<fC03 i1="03" i2="X" l="FRE">
<s0>Anticorps bispécifique</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="ENG">
<s0>Bispecific antibody</s0>
<s5>03</s5>
</fC03>
<fC03 i1="03" i2="X" l="SPA">
<s0>Anticuerpo biespecífico</s0>
<s5>03</s5>
</fC03>
<fC03 i1="04" i2="X" l="FRE">
<s0>Anticorps simple chaîne</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="ENG">
<s0>Single chain antibody</s0>
<s5>04</s5>
</fC03>
<fC03 i1="04" i2="X" l="SPA">
<s0>Anticuerpo simple cadena</s0>
<s5>04</s5>
</fC03>
<fC03 i1="05" i2="X" l="FRE">
<s0>Thérapie génique</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="ENG">
<s0>Gene therapy</s0>
<s5>05</s5>
</fC03>
<fC03 i1="05" i2="X" l="SPA">
<s0>Terapia génica</s0>
<s5>05</s5>
</fC03>
<fC03 i1="06" i2="X" l="FRE">
<s0>Tumeur maligne</s0>
<s5>14</s5>
</fC03>
<fC03 i1="06" i2="X" l="ENG">
<s0>Malignant tumor</s0>
<s5>14</s5>
</fC03>
<fC03 i1="06" i2="X" l="SPA">
<s0>Tumor maligno</s0>
<s5>14</s5>
</fC03>
<fC03 i1="07" i2="X" l="FRE">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>16</s5>
</fC03>
<fC03 i1="07" i2="X" l="ENG">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>16</s5>
</fC03>
<fC03 i1="07" i2="X" l="SPA">
<s0>Coronavirus</s0>
<s2>NW</s2>
<s5>16</s5>
</fC03>
<fC03 i1="08" i2="X" l="FRE">
<s0>Récepteur EGFR</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="08" i2="X" l="ENG">
<s0>Epidermal growth factor receptor</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC03 i1="08" i2="X" l="SPA">
<s0>Receptor EGFR</s0>
<s4>CD</s4>
<s5>96</s5>
</fC03>
<fC07 i1="01" i2="X" l="FRE">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="ENG">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="01" i2="X" l="SPA">
<s0>Coronaviridae</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="FRE">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="ENG">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="02" i2="X" l="SPA">
<s0>Nidovirales</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="FRE">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="ENG">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fC07 i1="03" i2="X" l="SPA">
<s0>Virus</s0>
<s2>NW</s2>
</fC07>
<fN21>
<s1>290</s1>
</fN21>
<fN44 i1="01">
<s1>OTO</s1>
</fN44>
<fN82>
<s1>OTO</s1>
</fN82>
</pA>
</standard>
</inist>
</record>

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