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 journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)56-67
Number of pages12
JournalVirology
Volume361
Issue number1
DOIs
Publication statusPublished - 25 Apr 2007

Cite this

Carette, Jan E ; Graat, Harm C A ; Schagen, Frederik H E ; Mastenbroek, D C Jeroen ; Rots, Marianne G ; Haisma, Hidde J ; Groothuis, Geny M M ; Schaap, Gerard R ; Bras, Johannes ; Kaspers, Gertjan J L ; Wuisman, Paul I J M ; Gerritsen, Winald R ; van Beusechem, Victor W. / A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor. In: Virology. 2007 ; Vol. 361, No. 1. pp. 56-67.
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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.",
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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}",
year = "2007",
month = "4",
day = "25",
doi = "10.1016/j.virol.2006.11.011",
language = "English",
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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

A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor. / Carette, Jan E; Graat, Harm C A; Schagen, Frederik H E; Mastenbroek, D C Jeroen; Rots, Marianne G; Haisma, Hidde J; Groothuis, Geny M M; Schaap, Gerard R; Bras, Johannes; Kaspers, Gertjan J L; Wuisman, Paul I J M; Gerritsen, Winald R; van Beusechem, Victor W.

In: Virology, Vol. 361, No. 1, 25.04.2007, p. 56-67.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - A conditionally replicating adenovirus with strict selectivity in killing cells expressing epidermal growth factor receptor

AU - Carette, Jan E

AU - Graat, Harm C A

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

PY - 2007/4/25

Y1 - 2007/4/25

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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KW - Antibodies/immunology

KW - Antibodies, Bispecific/immunology

KW - Antibodies, Viral/immunology

KW - Capsid Proteins/genetics

KW - Cells, Cultured

KW - Genetic Therapy/methods

KW - Genetic Vectors

KW - Humans

KW - Immunoglobulin Variable Region/immunology

KW - Mutation

KW - Neoplasms/therapy

KW - Oncolytic Virotherapy/methods

KW - Oncolytic Viruses/physiology

KW - Protein Binding

KW - Receptor, Epidermal Growth Factor/immunology

KW - Species Specificity

KW - Virus Replication

U2 - 10.1016/j.virol.2006.11.011

DO - 10.1016/j.virol.2006.11.011

M3 - Article

VL - 361

SP - 56

EP - 67

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SN - 0042-6822

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