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- Title
Preclinical study of an ex vivo gene therapy protocol for hepatocarcinoma.
- Authors
Lortal, B; Gross, F.; Peron, J. M.; Pénary, M.; Berg, D.; Hennebelle, I.; Favre, G.; Couderc, B.
- Abstract
Preclinical studies in several animal models as well as clinical trials have shown a reduction in tumor growth following immunotherapy with interleukin-12 (IL-12). This cytokine is appropriate to test in therapeutic clinical trials to treat hepatocarcinoma (HC), a pathology often associated with hepatitis B or C-induced cirrhosis. The local delivery into the liver would be achieved through ex vivo gene transfer using retroviral (rv) vectors in autologous fibroblast carriers. In support of this clinical trial, a rv vector has been constructed to express coordinately both chains p35 and p40 of human IL-12. Here, we have tested good manufacturing practices (GMP) clinical lots of viral vectors derived from the transfected packaging cell line, PG13rvIL-12. We have also devised methods to facilitate the isolation of fibroblasts from freshly harvested skin specimens, enhance their outgrowth in large-scale cultures and assay IL-12 production following transduction, without any selection and irradiation. Twenty-four human skin specimens were processed to obtain fibroblast suspensions that were typically maintained for up to 8 or 12 passages. The mean ±s.d. overall time for obtaining the required number of transduced cells for the highest IL-12 need was 40 days. The procedure, in accordance with the French medical agency for gene therapy clinical trials, is now ready to begin a clinical trial.Cancer Gene Therapy (2009) 16, 329–337; doi:10.1038/cgt.2008.88; published online 7 November 2008
- Subjects
LIVER cancer; GENE therapy; IMMUNOTHERAPY; CIRRHOSIS of the liver; FIBROBLASTS; ANIMAL models in research; CLINICAL trials
- Publication
Cancer Gene Therapy, 2009, Vol 16, Issue 4, p329
- ISSN
0929-1903
- Publication type
Article
- DOI
10.1038/cgt.2008.88