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

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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 αv 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 αv integrin blocking antibody. However, other human tumor lines expressing αv integrins were not transduced by virus with either the modified or unmodified capsid. We conclude that modification of the FPV capsid to bind αv 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.