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
- 1Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA
- 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.
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-
compared to rvv-lacZ-treated mice, while the levels of IL-4 and IL-5 were comparable. Numbers of IFN-
-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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