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  • Title: Tumor targeting of baculovirus displaying a lymphatic homing peptide.
    Author: Mäkelä AR, Enbäck J, Laakkonen JP, Vihinen-Ranta M, Laakkonen P, Oker-Blom C.
    Journal: J Gene Med; 2008 Sep; 10(9):1019-31. PubMed ID: 18655234.
    Abstract:
    BACKGROUND: Tumor-associated cells and vasculature express attractive molecular markers for site-specific vector targeting. To attain tumor-selective tropism, we recently developed a baculovirus vector displaying the lymphatic homing peptide LyP-1, originally identified by ex vivo/in vivo screening of phage display libraries, on the viral envelope by fusion to the transmembrane anchor of vesicular stomatitis virus G-protein. METHODS: In the present study, we explored the specificity and kinetics of viral binding and internalization as well as in vivo tumor homing of the LyP-1 displaying virus to elucidate the applicability of baculovirus for targeted therapies. RESULTS: We demonstrated that the LyP-1 peptide contributes to saturable binding of baculovirus in human MDA-MB-435 and HepG2 carcinoma cells and escalates the kinetics of viral internalization leading to earlier nuclear accumulation and enhanced transgene expression. The LyP-1 displaying virus also showed stronger competitiveness against transduction with wild-type baculovirus, suggesting involvement of a specific receptor in cellular attachment and entry. Following intravenous injections, the modified virus accumulated within the human MDA-MB-435 and MDA-MB-231 carcinoma xenografts in mice with higher specificity and efficiency than the control virus. Targeting of the modified virus was more specific in the MDA-MB-435 than in the MDA-MB-231 xenografts as demonstrated by higher tumor accumulation and lower distribution in nontarget organs. No apparent cytotoxicity was associated with the surface modification. CONCLUSIONS: This first demonstration of in vivo tumor targeting of a systemically administered, tropism-modified baculoviral vector highlights the potential of baculovirus-mediated targeted therapies.
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