Folate‐conjugated herpes simplex virus for retargeting to tumor cells

Abstract Background Herpes simplex virus type 1 (HSV‐1)‐mediated oncolytic therapy is a promising cancer treatment modality. However, viral tropism is considered to be one of the major stumbling blocks to the development of HSV‐1 as an anticancer agent. Methods The surface of oncolytic HSV‐1 G207 was covalently modified with folate‐poly (ethylene glycol) conjugate (FA‐PEG). The specificities and tumor targeting efficiencies of modified or unmodified G207 particles were analyzed by a real‐time polymerase chain reaction at the level of cell attachment and entry. Immune responses were assessed by an interleukin‐6 release assay from RAW264.7 macrophages. Biodistribution and in vivo antitumoral activity after intravenous delivery was evaluated in BALB/c nude mice bearing subcutaneous KB xenograft tumors. Results FA‐PEG‐HSV exhibited enhanced targeting specificity for folate receptor over‐expressing tumor cells and had lower immunogenicity than the unmodified HSV. In vivo , the FA‐PEG‐HSV group revealed an increased anti‐tumor efficiency and tumor targeting specificity compared to the naked HSV. Conclusions These results indicate that folate‐conjugated HSV G207 presents a folate receptor‐targeted oncolytic virus with a potential therapeutic value via retargeting to tumor cells.