A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

Jan E. Carette; Harm C.A. Graat; Frederik H.E. Schagen; D. C.Jeroen Mastenbroek; Marianne G. Rots; Hidde J. Haisma; Geny M.M. Groothuis; Gerard R. Schaap; Johannes Bras; Gertjan J.L. Kaspers; Paul I.J.M. Wuisman; Winald R. Gerritsen; Victor W. van Beusechem

doi:10.1016/j.virol.2006.11.011

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

Jan E. Carette, Harm C.A. Graat, Frederik H.E. Schagen, D. C.Jeroen Mastenbroek, Marianne G. Rots, Hidde J. Haisma, Geny M.M. Groothuis, Gerard R. Schaap, Johannes Bras, Gertjan J.L. Kaspers, Paul I.J.M. Wuisman, Winald R. Gerritsen, Victor W. van Beusechem

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.

Original language	English (US)
Pages (from-to)	56-67
Number of pages	12
Journal	Virology
Volume	361
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2006.11.011
State	Published - Apr 25 2007
Externally published	Yes

Keywords

Coxsackie and adenovirus receptor
Epidermal growth factor receptor
Gene therapy
Oncolytic adenovirus
Osteosarcoma
Targeting

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2006.11.011

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Carette, J. E., Graat, H. C. A., Schagen, F. H. E., Mastenbroek, D. C. J., Rots, M. G., Haisma, H. J., Groothuis, G. M. M., Schaap, G. R., Bras, J., Kaspers, G. J. L., Wuisman, P. I. J. M., Gerritsen, W. R., & van Beusechem, V. W. (2007). A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor. Virology, 361(1), 56-67. https://doi.org/10.1016/j.virol.2006.11.011

Carette, JE, Graat, HCA, Schagen, FHE, Mastenbroek, DCJ, Rots, MG, Haisma, HJ, Groothuis, GMM, Schaap, GR, Bras, J, Kaspers, GJL, Wuisman, PIJM, Gerritsen, WR & van Beusechem, VW 2007, 'A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor', Virology, vol. 361, no. 1, pp. 56-67. https://doi.org/10.1016/j.virol.2006.11.011

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title = "A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor",

abstract = "Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.",

keywords = "Coxsackie and adenovirus receptor, Epidermal growth factor receptor, Gene therapy, Oncolytic adenovirus, Osteosarcoma, Targeting",

author = "Carette, {Jan E.} and Graat, {Harm C.A.} and Schagen, {Frederik H.E.} and Mastenbroek, {D. C.Jeroen} and Rots, {Marianne G.} and Haisma, {Hidde J.} and Groothuis, {Geny M.M.} and Schaap, {Gerard R.} and Johannes Bras and Kaspers, {Gertjan J.L.} and Wuisman, {Paul I.J.M.} and Gerritsen, {Winald R.} and {van Beusechem}, {Victor W.}",

note = "Funding Information: The authors wish to thank Maarten J.H. Slooff (Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery at the University Hospital Groningen) for providing human liver samples. Marjolein van Miltenburg is acknowledged for technical assistance. This research was supported by grants from the VU University Stimulation Fund (USF), the Pasman Foundation and by a research fellowship of the Royal Netherlands Academy of Arts and Sciences (KNAW) to Victor van Beusechem.",

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doi = "10.1016/j.virol.2006.11.011",

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AU - Carette, Jan E.

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AU - Schagen, Frederik H.E.

AU - Mastenbroek, D. C.Jeroen

AU - Rots, Marianne G.

AU - Haisma, Hidde J.

AU - Groothuis, Geny M.M.

AU - Schaap, Gerard R.

AU - Bras, Johannes

AU - Kaspers, Gertjan J.L.

AU - Wuisman, Paul I.J.M.

AU - Gerritsen, Winald R.

AU - van Beusechem, Victor W.

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PY - 2007/4/25

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N2 - Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.

AB - Virotherapy of cancer using oncolytic adenoviruses has shown promise in both preclinical and clinical settings. One important challenge to reach the full therapeutic potential of oncolytic adenoviruses is accomplishing efficient infection of cancer cells and avoiding uptake by normal tissue through tropism modification. Towards this goal, we constructed and characterized an oncolytic adenovirus, carrying mutated capsid proteins to abolish the promiscuous adenovirus native tropism and encoding a bispecific adapter molecule to target the virus to the epidermal growth factor receptor (EGFR). The new virus displayed a highly selective targeting profile, with reduced infection of EGFR-negative cells and efficient killing of EGFR-positive cancer cells including primary EGFR-positive osteosarcoma cells that are refractory to infection by conventional adenoviruses. Our method to modify adenovirus tropism might thus be useful to design new oncolytic adenoviruses for more effective treatment of cancer.

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A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

Abstract

Keywords

ASJC Scopus subject areas

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