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Combination Gene Therapy Using IL-2 and GM-CSF Genes Transferred by a Defective Infectious Single Cycle Herpes Virus (DISC Virus) in Head and Neck Squamous Cell Cancer Model / 대한이비인후과학회지
Article in Korean | WPRIM | ID: wpr-648069
Responsible library: WPRO
ABSTRACT
BACKGROUND AND

OBJECTIVES:

The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is an attenuated virus originally produced as a viral vaccine, but it also serves as an efficient gene transfer vehicle. The main goals of this study were to examine determinants of gene transfer using DISC vectors for squamous cell carcinoma and to evaluate the efficacy of vaccination with the DISC virus carrying a combination of immunomodulatory genes (IL-2, GM-CSF) as cancer therapy in a model of squamous cell cancer in the C3H/HeJ mice. MATERIALS AND

METHODS:

We determinated the gene and protein expression of DISC-IL-2 and DISC-GM-CSF transfected SCCVII cells by RT-PCR and ELISA method. Also, we evaluated the ex vivo vaccination effects of DISC-IL-2 and DISC-GMCSF on preventing the development of SCCVII tumor.

RESULTS:

SCCVII cells transduced by the DISC virus vector (MOI=10) carrying the IL-2, or the GM-CSF gene, produced nanogram quantities of IL-2 or GM-CSF per 10(6) cells. Of particular interest was the observation that cells irradiated at different doses (5,000 cGy, 10,000 cGy) secreted levels of GM-CSF or IL-2 that were comparable to non-irradiated cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-IL-2 or DISC-GMCSF resulted in protection against subsequent tumor challenge (p<0.01). Among the multiple immunomodulatory transgenes vaccination groups, the DISC-GMCSF transfected vaccine showed the greatest suppression of tumor development and growth (p<0.001).

CONCLUSION:

These data demonstrate that 1) The DISC virus vector is capable of efficient gene transfer to SCCVII cells, 2) The GM-CSF secreting, genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor cell challenge and suppressed tumor growth in our tumor model. The DISC virus-mediated, cytokine gene transfer may prove to be useful in clinical therapy for head and neck cancers.
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Enzyme-Linked Immunosorbent Assay / Carcinoma, Squamous Cell / Genetic Therapy / Granulocyte-Macrophage Colony-Stimulating Factor / Interleukin-2 / Vaccination / Neoplasms, Squamous Cell / Transgenes / Growth and Development / Head Language: Korean Journal: Korean Journal of Otolaryngology - Head and Neck Surgery Year: 2001 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Enzyme-Linked Immunosorbent Assay / Carcinoma, Squamous Cell / Genetic Therapy / Granulocyte-Macrophage Colony-Stimulating Factor / Interleukin-2 / Vaccination / Neoplasms, Squamous Cell / Transgenes / Growth and Development / Head Language: Korean Journal: Korean Journal of Otolaryngology - Head and Neck Surgery Year: 2001 Type: Article