Inhibition of metastatic tumor growth in nude mice by portal vein infusions of matrix-targeted retroviral vectors bearing a cytocidal cyclin G1 construct

Tumor Invasion and associated angiogenesis evoke a remodeling of extracellu lar matrix components. Retroviral vectors hearing auxiliary matrix-targetin g motifs (i.e., collagen-binding polypeptides) accumulate at sites of newly exposed collagen, thus promoting tumor site specific gene delivery. In thi s study, we assessed the antitumor effects of serial portal vein infusions of matrix-targeted vectors bearing a mutant cyclin G1 (dnG1) construct in a nude mouse model of liver metastasis. The size of tumor fod was dramatical ly reduced in dnG1 vector-treated mice compared with that in control vector - or PBS-treated animals (P = 0.0002), These findings represent a definitiv e advance in the development of targeted Injectable vectors for metastatic cancer.