Korean Journal of Head & Neck Oncology (대한두경부종양학회지)

The Korean Society for Head and Neck Oncology (대한두경부종양학회)
권호 표지

Gene Therapy Using GM-CSF Gene Transferred by a Defective Infectious Single-cycle Herpes Virus in Micro-residual Organotropic Head and Neck Squamous Cell Cancer Model

향장기성 두경부 편평세포암종의 미세잔존암 모델에서 GM-CSF 유전자를 이입시킨 제한복제성 헤르페스바이러스 벡터를 이용한 종양백신의 유전자 치료

  • Kim Se-Heon (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Choi Eun-Chang (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Kim Han-Su (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Chang Jung-Hyun (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Kim Ji-Hoon (Department of Otorhinolaryngology, Yonsei University College of Medicine) ;
  • Kim Kwang-Moon (Department of Otorhinolaryngology, Yonsei University College of Medicine)
  • 김세헌 (연세대학교 의과대학 이비인후과학교실) ;
  • 최은창 (연세대학교 의과대학 이비인후과학교실) ;
  • 김한수 (연세대학교 의과대학 이비인후과학교실) ;
  • 장정현 (연세대학교 의과대학 이비인후과학교실) ;
  • 김지훈 (연세대학교 의과대학 이비인후과학교실) ;
  • 김광문 (연세대학교 의과대학 이비인후과학교실)
  • Published : 2003.05.01
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Abstract

Background and Objectives: The Herpes Simplex type 2 Defective Infectious Single Cycle virus (DISC virus) is attenuated virus originally produced as viral vaccines but are also efficient gene transfer vehicle. The main goals of this study were to examine the efficiencies of the gene transfer using DISC vectors for various head and neck squamous cell carcinoma cell lines and to evaluate the efficacy of vaccination with DISC virus carrying a immunomodulatory genes (GM-CSF) as cancer therapy in a organotopic oral cavity squamous cell cancer model. Materials and Methods : We determinated the gene transfer efficiency of DISC virus by x-gal stain method and proved gene and protein expression of DISC-GMCSF transfected SCCVII cells by RT-PCR and ELISA method. Also we evaluated the ex vivo vaccination effects of SCCVII/GMCSF (DISC-GMCSF transfected SCCVII vaccine) vaccine on preventing the recurrence of micro-residual tumor. After the vaccination of SCCVII/GMCSF, specific cytotoxic T-cell responses was evaluated by CTL assay. Results: At an MOI of 10 DISC virus showed 64-88% of transfection rates in various head and neck squamous cancer cell lines. SCCVII cells transduced by DISC virus vector (MOI=10) carrying the GM-CSF gene, produced 4.5 nanogram quantities of GM-CSF per $10^6$ cells. In vivo vaccination using tumor cells transduced ex vivo with DISC-GMCSF resulted in better protection rate against subsequent tumor recurrence in organotopic oral cavity cancer model. Although tumor free survival rate was not statistically significantly increased in vaccination group (p=0.078), tumor specific cytotocic T-cell responses were significantly increased in SCCVII/GMCSF vaccination group. Conclusion: These data demonstrate that; 1) The DISC virus vector is capable of efficient gene transfer to various head and neck squamous cancer cell lines, 2) GM-CSF secreting genetically modified tumor vaccine (SCCVII/GMCSF) efficiently protected against tumor recurrence in organotopic micro-residual oral cavity cancer model and produced tumor specific cytotoxic T-cell response. DISC virus-mediated, cytokine gene transfer may prove to be useful as a clinical therapy for head and neck cancers.

Keywords

References

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