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

Masahiro Toda, R. L. Martuza, S. D. Rabkin

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 dvIL-12-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 vectors are particularly well suited to this because they can accommodate the insertion of large and multiple gene sequences.

Original languageEnglish
Pages (from-to)332-339
Number of pages8
JournalGene Therapy
Volume8
Issue number4
DOIs
Publication statusPublished - 2001

Fingerprint

Defective Viruses
Cancer Vaccines
Simplexvirus
Interleukin-12
Genetic Therapy
Suicide
Ganciclovir
Cytokines
Thymidine Kinase
Neoplasms
Helper Viruses
Therapeutics
Human Herpesvirus 1
Virus Diseases
Growth
Genes
Colon
Adenocarcinoma
Escherichia coli

Keywords

  • Cancer vaccine
  • CT26 adenocarcinoma
  • HSV
  • IL-12
  • Thymidine kinase

ASJC Scopus subject areas

  • Genetics

Cite this

Combination suicide/cytokine gene therapy as adjuvants to a defective herpes simplex virus-based cancer vaccine. / Toda, Masahiro; Martuza, R. L.; Rabkin, S. D.

In: Gene Therapy, Vol. 8, No. 4, 2001, p. 332-339.

Research output: Contribution to journalArticle

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