Original Article

Molecular Therapy (2006) 13, 183–193; doi: 10.1016/j.ymthe.2005.06.481

Recombinant Vaccinia Virus Expressing Interleukin-2 Invokes Anti-tumor Cellular Immunity in an Orthotopic Murine Model of Head and Neck Squamous Cell Carcinoma

Santanu Dasgupta1, Malaya Bhattacharya-Chatterjee1, Bert W. O'Malley Jr.2 and Sunil K. Chatterjee1

  1. 1Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA
  2. 2Department of Otolaryngology–Head and Neck Surgery, University of Pennsylvania Health System, Philadelphia, PA 19104, USA

Correspondence: Sunil K. Chatterjee, Fax: +1 513 558 0505. E-mail: sunil.chatterjee@uc.edu

Received 11 April 2005; Revised 18 May 2005; Accepted 11 June 2005.

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Abstract

Induction of T cell immunity following vaccination with a recombinant vaccinia virus expressing interleukin-2 (rvv-IL-2) was studied in an orthotopic murine model (SCCVII/SF) of head and neck squamous cell carcinoma (HNSCC). Mice bearing SCCVII/SF cells in the oral cavity were vaccinated subcutaneously with irradiated, rvv-IL-2-infected tumor cells combined with intratumoral injection of rvv-IL-2, resulting in recruitment of larger numbers of CD3+ CD8+ and CD3+ CD4+ T cells in the spleen (Sp) and tumor-draining lymph nodes (TDLN) compared to control vaccine rvv-lacZ. Tumor-specific CD8+ T and CD4+ helper T cell activities in the Sp and TDLN were significantly increased in rvv-IL-2-treated mice. Sp and TDLN cells from rvv-IL-2-treated mice secreted significantly higher levels of IL-2 and IFN-gamma compared to rvv-lacZ-treated mice, while the levels of IL-4 and IL-5 were comparable. Numbers of IFN-gamma-secreting cells were also higher in rvv-IL-2-treated mice. Vaccine efficiency was completely abolished by depletion of CD8+/CD4+ T cells from rvv-IL-2-vaccinated mice. We conclude that anti-tumor activities of rvv-IL-2 are due to the induction of tumor-specific CD8+ CTL and CD4+ Th1-type helper T cells, and rvv-IL-2 may be used for treatment of HNSCC patients, since SCC VII/SF closely resembles HNSCC.

Keywords:

head and neck cancer, immunotherapy, vaccinia virus, interleukin-2, CD4+/CD8+ T cells

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