Augmentation of Antitumor Immune Responses by Multiple Intratumoral Inoculations of Replication-Conditional HSV and Interleukin-12

Yukihiko Iizuka, Ayuko Suzuki, Yutaka Kawakami, Masahiro Toda

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Intratumoral inoculation with a herpes simplex virus (HSV) mutant, G207, as an in situ cancer vaccine has been shown to inhibit tumor growth by inducing tumor-specific immune responses. Here, as a step toward the clinical application of this therapeutic approach, we evaluated different protocols for enhancing the antitumor effect. First, in a bilaterally established tumor model with CT26 colon carcinoma, we demonstrated that multiple intratumoral inoculations with G207 induced a greater antitumor effect on both the inoculated and distant tumors than did 1 or 2 inoculations. Second, to boost this antitumor effect, we developed 2 strategies: multiple in situ cancer vaccines with G207 in combination with systemic administration of recombinant interleukin-12 (rIL-12) (G207/systemic rIL-12) or local administration of rIL-12 (G207/local rIL-12). The antitumor effects in both the inoculated and distant tumors by the combined treatments were significantly greater than by either G207 or rIL- 12 treatment alone. G207/systemic rIL-12 and G207/local rIL-12 mediated the complete regression of both the inoculated and distant tumors in 67% and 79% of the animals, respectively. These results indicate that multiple intratumoral inoculations of G207 and systemic or local rIL- 12 administration work synergistically to facilitate tumor regression and that this combination of treatments may have potential for treating cancer metastasis.

Original languageEnglish
Pages (from-to)92-98
Number of pages7
JournalJournal of Immunotherapy
Volume27
Issue number2
DOIs
Publication statusPublished - 2004 Jan 1

Keywords

  • G207,1L-12
  • Herpes simplex virus
  • Intratumoral inoculation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Pharmacology
  • Cancer Research

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