Transduction of murine and human tumors using recombinant adenovirus vectors.

Abstract:

BACKGROUND:Most cytokine-based cancer gene therapy clinical trials have used labor-intensive, retrovirus-mediated strategies resulting in unpredictable gene expression. Recombinant AdV vectors were evaluated for easier, more reproducible gene transfer into 12 human melanoma, 2 murine fibrosarcomas, and 8 other tumor cell lines. METHODS:AdV vectors contained a reporter (Escherichia coli beta-galactosidase or firefly luciferase) or cytokine gene (human interleukin-2 [IL-2] or IL-7). Transduction efficiencies and expression levels were assessed by histochemical staining, flow cytometry, polymerase chain reaction, fluorometry, and enzyme-linked immunosorbent assay. Tumorigenicity was determined by subcutaneous injection of cells into syngeneic mice. RESULTS:All cell lines studied were transduced with AdV. Most cell lines exhibited 100% transduction efficiencies (by flow cytometry) at multiplicities of infection (MOI) epsilon 10. Gene expression correlated linearly with MOI, but a cytopathic effect was observed at MOI > 100 with all vectors. Nanogram gene expression levels were routinely achieved. Irradiation (30 Gy) minimally affected expression levels. Tumorigenicity of AdV-IL-2-transduced fibrosarcoma cells in mice was inversely related to IL-2 production. A majority of mice that rejected their tumor challenge were immune to tumor rechallenge. CONCLUSIONS:E1-deleted AdV vectors may prove useful in generating tumor vaccines ex vivo with high, transient cytokine expression levels.

journal_name

Ann Surg Oncol

authors

Toloza EM,Hunt K,Miller AR,McBride W,Lau R,Swisher S,Rhoades K,Arthur J,Choi J,Chen L,Chang P,Chen A,Glaspy J,Economou JS

doi

10.1007/BF02316813

subject

Has Abstract

pub_date

1997-01-01 00:00:00

pages

70-9

issue

1

eissn

1068-9265

issn

1534-4681

journal_volume

4

pub_type

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