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 extracellular matrix components. Retroviral vectors bearing auxiliary matrix-targeting motifs (ie., 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.
Gordon
E M
EM
Department of Colorectal Surgery, Gene Therapy Laboratories, Los Angeles, California 90089, USA. emgordon@genome2.hsc.usc.edu
Liu
P X
PX
Chen
Z H
ZH
Liu
L
L
Whitley
M D
MD
Gee
C
C
Groshen
S
S
Hinton
D R
DR
Beart
R W
RW
Hall
F L
FL
D016475:3T3 Cells; D000818:Animals; D002460:Cell Line; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007262:Infusions, Intravenous; D008113:Liver Neoplasms / Q000473:pathology / Q000517:prevention & control / Q000556:secondary*; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000473:pathology* / Q000628:therapy*; D011169:Portal Vein; D012190:Retroviridae
C534702:CCNG1 protein, human; C534703:Ccng1 protein, mouse; D056746:Cyclin G; D056766:Cyclin G1; D016213:Cyclins