Recombinant vaccinia virus expressing interleukin-2 invokes anti-tumor cellular immunity in an orthotopic murine model of head and neck squamous cell carcinoma.
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.
Dasgupta
Santanu
S
Department of Internal Medicine and the Barrett Cancer Center, University of Cincinnati, Cincinnati, OH 45267, USA.
Bhattacharya-Chatterjee
Malaya
M
O'Malley
Bert W
BW
Chatterjee
Sunil K
SK
D000279:Administration, Cutaneous; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D045744:Cell Line, Tumor; D003602:Cytotoxicity, Immunologic; D004195:Disease Models, Animal; D005260:Female; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D007111:Immunity, Cellular; D015552:Injections, Intralesional; D007376:Interleukin-2 / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D011995:Recombination, Genetic; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology; D014616:Vaccinia virus / Q000235:genetics*
D019496:Cancer Vaccines; D015395:Histocompatibility Antigens Class I; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell