Combination suicide/cytokine gene therapy as adjuvants to a defective herpes simplex virus-based cancer vaccine

Gene Therapy
M TodaS D Rabkin

Abstract

We have used syngeneic, established bilateral subcutaneous tumor models to examine the antitumor activity of herpes simplex virus (HSV) vectors, including the induction of an immune response against non-inoculated distant tumors. In such a model with CT26 murine colon adenocarcinoma, unilateral intratumoral inoculation of replication-deficient HSV-1 tsK inhibited the growth of both the inoculated and noninoculated established tumors. To enhance this limited antitumor immune response, we generated a defective HSV vector, dvIL12-tk encoding both interleukin-12 (IL-12) and HSV thymidine kinase (TK), with tsK as the helper virus. In a 'suicide gene' strategy, ganciclovir (GCV) treatment after intratumoral inoculation of dvlacZ-tk/tsK, encoding E. coli lacZ instead of IL-12, resulted in enhanced antitumor activity. Antitumor activity was also enhanced by local expression of IL-12 from dvIL12-tk/tsK. The combination of IL-12 cytokine therapy with GCV treatment was the most efficacious approach, with significantly greater inhibition of tumor growth than IL-12 or TK + GCV alone. These results illustrate the power of combining different cancer therapy approaches; 'suicide gene' therapy, cytokine therapy, and HSV vector infection. HSV ve...Continue Reading

References

Jan 1, 1992·Brain Research. Molecular Brain Research·P A JohnsonT Friedmann
Aug 25, 1989·The Medical Letter on Drugs and Therapeutics
Jan 1, 1995·Annual Review of Immunology·D M Pardoll
Mar 28, 1995·Proceedings of the National Academy of Sciences of the United States of America·S H ChenS L Woo
Mar 14, 1995·Proceedings of the National Academy of Sciences of the United States of America·Y NoguchiL J Old
Nov 1, 1993·Current Opinion in Oncology·J W Mier, M B Atkins
Jan 16, 1996·Journal of Immunological Methods·V L WilkinsonD H Presky
Sep 3, 1996·Proceedings of the National Academy of Sciences of the United States of America·A Y HuangE M Jaffee
Feb 15, 1997·The Journal of Clinical Investigation·H M KarpoffY Fong
Feb 10, 2000·Annals of the New York Academy of Sciences·E M Jaffee
Mar 8, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·I NarvaizaJ Prieto
Apr 5, 2000·The Journal of Clinical Investigation·R L Martuza
Aug 10, 2000·Neoplasia : an International Journal for Oncology Research·A JacobsC Fraefel
Oct 6, 2000·Molecular Therapy : the Journal of the American Society of Gene Therapy·M TodaS D Rabkin

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Citations

Oct 19, 2005·Gene Therapy·R ArgnaniR Manservigi
Oct 15, 2013·International Journal of Nanomedicine·Shengli DongGaopeng Li
Mar 7, 2008·World Journal of Gastroenterology : WJG·Yan-Xia MiYun-Chun Li
Jan 14, 2016·Artificial Cells, Nanomedicine, and Biotechnology·Saiedeh Razi SoofiyaniBehzad Baradaran
May 29, 2012·Cancer Letters·Sónia DuarteValérie Pierrefite-Carle
Mar 17, 2010·International Journal of Cancer. Journal International Du Cancer·Kozo Ohkusu-TsukadaMasahiro Toda
May 25, 2002·Cancer Treatment Reviews·J M KaminskiA Pollack
Sep 3, 2005·Cancer Gene Therapy·S E LawlerE A Chiocca
Nov 22, 2005·Oncogene·J Michael MathisDavid T Curiel
Apr 11, 2006·Cancer Gene Therapy·Y Shen, J Nemunaitis
Mar 17, 2007·International Review of Psychiatry·Ian B KerrGlenys D Parry
Mar 26, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Aparajita KhatriPamela J Russell

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