Expansion of tropism of a feline parvovirus to target a human tumor cell line by display of an alpha(v) integrin binding peptide on the capsid.
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.
Maxwell
I H
IH
Department of Dermatology and University of Colorado Cancer Center, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Chapman
J T
JT
Scherrer
L C
LC
Spitzer
A L
AL
Leptihn
S
S
Maxwell
F
F
Corsini
J A
JA
D015703:Antigens, CD / Q000378:metabolism; D001943:Breast Neoplasms / Q000628:therapy; D002213:Capsid / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics; D004730:Endothelium, Vascular; D028301:Feline Panleukopenia Virus / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D018390:Gene Targeting / Q000379:methods; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D039482:Integrin alpha5; D015603:Keratinocytes; D008113:Liver Neoplasms / Q000628:therapy; D008156:Luciferases / Q000235:genetics; D008545:Melanoma / Q000628:therapy; D010051:Ovarian Neoplasms / Q000628:therapy; D016133:Polymerase Chain Reaction; D012208:Rhabdomyosarcoma / Q000628:therapy*; D012878:Skin Neoplasms / Q000628:therapy; D014161:Transduction, Genetic / Q000379:methods*; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D002352:Carrier Proteins; D039482:Integrin alpha5; D008156:Luciferases