Targeting human glioma cells using HSV-1 amplicon peptide display vector

Abstract

Targeting cell infection using herpes simplex virus type 1 (HSV-1) vectors is a complicated issue as the process involves multiple interactions of viral envelope glycoproteins and cellular host surface proteins. In this study, we have inserted a human glioma-specific peptide sequence (denoted as MG11) into a peptide display HSV-1 amplicon vector replacing the heparan sulfate-binding domain of glycoprotein C (gC). The modified MG11:gC envelope recombinant vectors were subsequently packaged into virions in the presence of helper virus deleted for gC. Our results showed that the tropism of these HSV-1 recombinant virions was increased for human glioma cells in culture as compared with wild-type virions. The binding of these recombinant virions could also be blocked effectively by preincubating the cells with the glioma-specific peptide, indicating that MG11 peptide and the recombinant virions competed for the same or similar receptor-binding sites on the cell surface of human glioma cells. Furthermore, preferential homing of these virions was shown in xenograft glioma mouse model following intravascular delivery. Taken together, these results validated the hypothesis that HSV-1 binding to cells can be redirected to human gliomas through the incorporation of MG11 peptide sequence to the virions.

Oncolytic herpes simplex virus tumor targeting and neutralization escape by engineering viral envelope glycoproteins

“…reported that HSV-1 was retargeted to a specific receptor IL13Rα2 expressed in malignant glioma, by ablating the HS-binding sites of gB and gC, and the insertion of IL-13 in the N-terminal of gC and gD, but the recombinant virus can still infect normal cells by interaction with HVEM or nectin 1 (Zhou et al., 2002 ). The glycoprotein gC can also be retargeted to the human glioma cells through the ligand human glioma-specific peptide sequence (denoted as MG11) (Ho et al., 2010 ).…”