Gene therapy for head and neck cancer using vaccinia virus expressing IL-2 in a murine model, with evidence of immune suppression

Hongxing Qin, Joseph Valentino, Subha Manna, Pulak K. Tripathi, Malaya Bhattacharya-Chatterjee, Kenneth A. Foon, Bert W. O'Malley, Sunil K. Chatterjee

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

We evaluated the efficiency of recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) as a tumor vaccine in an immunocompetent mouse model of head and neck squamous cell carcinoma (SCC VII/SF). Mice with five-day-old tumors in the floor of the mouth were treated with rvv-IL-2 by intratumoral injections. These treated mice survived longer (P < .03) than mice treated with control vaccines. Splenocytes, bone marrow, and lymph node cells from tumor-bearing mice responded poorly to concanavalin A stimulation, suggesting induction of immunosuppression. The rvv-IL-2 virus grew for 7 days in the tumor following intratumoral injection. We did not detect any virus particles in several normal organs following rvv-IL-2 injection. Comparison of expression levels of several potential immune inhibitory mediators between the tumors growing in mice and cultured tumor cells demonstrated higher expression of IL-10, GM-CSF, TGF-β, and NO synthetase in tumors. These results suggested possible roles for these molecules in immunosuppression. We conclude that rvv-IL-2 has potential as a therapeutic vaccine for head and neck cancer and that it can be more effective provided the immunosuppression is reversed.

Original languageEnglish
Pages (from-to)551-558
Number of pages8
JournalMolecular Therapy
Volume4
Issue number6
DOIs
StatePublished - 2001

Bibliographical note

Funding Information:
We thank Bernard Moss (National Institutes of Health) for the recombinant vaccinia virus, vCF13. This research was supported in part by NIH grant CA 89748 from the National Cancer Institute.

Keywords

  • Head and neck squamous cell carcinoma
  • IL-2
  • Immune suppression
  • Tumor vaccine
  • Vaccinia virus

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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