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Inhibition of Metastatic Tumor Growth in Nude Mice by Portal Vein Infusions of Matrix-targeted Retroviral Vectors Bearing a Cytocidal Cyclin G1 Construct¹

Departments of Colorectal Surgery [E. M. G., P. X. L., Z. H. C., L. L., M. D. W., R. W. B., F. L. H.], Pediatrics [E. M. G.,], and Pathology [D. R. H.], Gene Therapy Laboratories [E. M. G., P. X. L., Z. H. C., L. L., M. D. W., F. L. H.]; Norris Comprehensive Cancer Center Biostatistics Core [C. G., S. G.]; and University of Southern California School of Medicine [E. M. G., P. X. L., Z. H. C., L. L., M. D. W., C. G., S. G., R. W. B., F. L. H.], Los Angeles, California 90089

Tumor invasion and associated angiogenesis evoke a remodeling of extracellular matrix components. Retroviral vectors bearing auxiliary matrix-targeting motifs (i.e., collagen-binding polypeptides) accumulate at sites of newly exposed collagen, thus promoting tumor site-specific gene delivery. In this 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 foci was dramatically reduced in dnG1 vector-treated mice compared with that in control vector- or PBS-treated animals (P = 0.0002). These findings represent a definitive advance in the development of targeted injectable vectors for metastatic cancer.

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