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Granulocyte‐Macrophage Colony‐Stimulating Factor in a Combination Gene Therapy Strategy for Head and Neck Cancer
Author(s) -
Day Katherine V.,
Li Daqing,
Liu Shixi,
Guo Ming,
O'Malley Bert W.
Publication year - 2001
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1097/00005537-200105000-00009
Subject(s) - immunogenicity , head and neck squamous cell carcinoma , genetic enhancement , immunology , immunotherapy , cd8 , medicine , granulocyte macrophage colony stimulating factor , cancer research , major histocompatibility complex , cancer , antigen , immune system , biology , cytokine , head and neck cancer , gene , biochemistry
Objectives/Hypothesis Gene therapy offers a new approach for treatment of head and neck squamous cell carcinoma (HNSCC). This study examined the effectiveness of granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) in combination gene therapy strategy against HNSCC in an orthotopic mouse model. Study Design Experimental animal research. Methods Established tumors were treated with recombinant adenovirus constructs containing the genes for murine granulocyte‐macrophage colony‐stimulating factor (Ad‐mGM‐CSF), murine interleukin 2 (Ad‐mIL‐2), or herpes simplex virus thymidine kinase (Ad‐tk). Results The combination of Ad‐mGM‐CSF or Ad‐mIL‐2 and Ad‐tk resulted in significantly greater reduction in tumor size versus other treatment groups or control subjects. There was no statistical significance between the triple combination of Ad‐mGM‐CSF, Ad‐mIL‐2, and Ad‐tk versus Ad‐mIL‐2 and Ad‐tk at 1 to 2 weeks after treatment. There was no tumor reduction seen from Ad‐mGM‐CSF alone and no additional benefit seen from Ad‐mGM‐CSF combinations in long‐term follow‐up studies. The greatest cytotoxic T‐lymphocyte and natural killer cell activity occurred in the combination Ad‐mIL‐2 and Ad‐tk groups with and without Ad‐mGM‐CSF. Conclusion Results suggest that the additional mGM‐CSF did not enhance the immunogenicity of the HNSCC. Optimal activation of T lymphocytes may require additional co‐stimulatory molecules to stabilize the interaction of the T lymphocyte and antigen presenting cell. The presence of major histocompatibility complex Class II may increase CD4 + T‐cell mediated immunogenicity and augment therapeutic antitumor immune responses in combination with tk, mIL‐2, and mGM‐CSF.