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

Gene Therapy
I H MaxwellJ Corsini

Abstract

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.

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Citations

Nov 5, 2002·Methods : a Companion to Methods in Enzymology·Ian H MaxwellFrançoise Maxwell
Jan 29, 2003·Journal of Virology·Wen YanYuqiao Shen
Dec 4, 2003·Expert Opinion on Biological Therapy·S FruehaufS Laufs
May 12, 2011·Reviews in Medical Virology·Danijela Koppers-Lalic, Rob C Hoeben
Jun 4, 2013·The American Journal of Clinical Hypnosis·Ernest RossiKathryn Rossi
Jan 18, 2008·Journal of Neurophysiology·Kyle HackerKathryn Medler
Jul 12, 2019·Frontiers in Microbiology·Joseph OngrádiDharam V Ablashi
Apr 9, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Julia Fakhiri, Dirk Grimm

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