Expansion of tropism of a feline parvovirus to target a human tumor cell line by display of an αv integrin binding peptide on the capsid
| Autor: | J.T. Chapman, AL Spitzer, Sebastian Leptihn, Françoise Maxwell, Ian H. Maxwell, JA Corsini, L.C. Scherrer |
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| Rok vydání: | 2001 |
| Předmět: |
Keratinocytes
Skin Neoplasms viruses Integrin Gene Expression Breast Neoplasms Integrin alpha5 Feline panleukopenia Recombinant virus Polymerase Chain Reaction Virus Transduction (genetics) Capsid Antigens CD Transduction Genetic Rhabdomyosarcoma Tumor Cells Cultured Genetics Humans Luciferases Melanoma Molecular Biology Ovarian Neoplasms biology Parvovirus Liver Neoplasms Genetic Therapy biology.organism_classification Virology Oncolytic virus Gene Targeting Carcinoma Squamous Cell biology.protein Molecular Medicine Female Endothelium Vascular Feline Panleukopenia Virus Carrier Proteins |
| Zdroj: | Gene Therapy. 8:324-331 |
| ISSN: | 1476-5462 0969-7128 |
| DOI: | 10.1038/sj.gt.3301399 |
| Popis: | The autonomous parvoviruses are small, non-enveloped, single strand DNA viruses. They occur in many species and they have oncolytic properties. We are modifying the capsid of feline panleukopenia virus (FPV), a parvovirus which normally infects feline cells, with the goal of targeting human tumor cells for potential cancer therapy. Using recombinant viruses transducing a luciferase reporter, we show that insertion of a cyclically constrained, integrin-binding peptide at an exposed position on the FPV capsid enables transduction of an alpha(v) integrin-expressing human rhabdomyosarcoma cell line (Rh18A). These cells were not transduced by virus with the unmodified FPV capsid. Transduction of Rh18A was specifically inhibited by an alpha(v) integrin blocking antibody. However, other human tumor lines expressing alpha(v) integrins were not transduced by virus with either the modified or unmodified capsid. We conclude that modification of the FPV capsid to bind alpha(v) integrins can contribute to, but is not generally sufficient for, redirecting infection to human tumor cells. The permissiveness of Rh18A cells presumably involves additional factors unique to this line among various human cell lines tested. |
| Databáze: | OpenAIRE |
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