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Pathogenesis of human papilloma virus type 16 E6 in tonsil squamous cell carcinoma
Reports NRF is supported by Research Projects( Pathogenesis of human papilloma virus type 16 E6 in tonsil squamous cell carcinoma | 2007 Year 신청요강 다운로드 PDF다운로드 | 이동욱(충북대학교) ) data is submitted to the NRF Project Results
Researcher who has been awarded a research grant by Humanities and Social Studies Support Program of NRF has to submit an end product within 6 months(* depend on the form of business)
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Project Number E00043
Year(selected) 2007 Year
the present condition of Project 종료
State of proposition 재단승인
Completion Date 2008년 08월 05일
Year type 결과보고
Year(final report) 2008년
Research Summary
  • Korean
  • 연구목적: 두경부암의 60% 이상이 HPV와 관련되며, 이러한 두경부암은 바이러스성 암단백질을 발현한다. 그러므로 이러한 단백질에 대한 백신을 이용하여 HPV 양성 두경부암의 발생을 예방하고자 하였다.
    연구방법: 아데노바이러스 조합 백신을 개발하여 HPV16 E6/E7 (Ad5 E6/E7)을 고안하였고, 이것을 쥐에 흡입시킨 후 두경부암세포를 이식하였다.
    연구결과: HPV16 E6/E7 (Ad5 E6/E7)을 흡입한 쥐에게 두경부암세포를 이식시킨 결과, 종양이 전혀 발생하지 않았다. 그러나, 정상대조군의 경우에는 두경부암세포를 이식시킨 결과, 종양이 발생하였다. 이들 쥐에 대한 비장 세포를 적출하여 IFN-γ의 생성을 확인한 결과, 백신치료를 받은 쥐의 비장세포에서 IFN-γ의 발생이 유의하게 증가함을 확인하였다.
    고찰: HPV16 E6/E7 (Ad5 E6/E7)은 두경부암 발생의 예방에 탁월한 효과가 있음을 실험적으로 증명하였으며, 그 기전은 IFN-γ를 통한 세포면역기능의 항진에 기인함을 확인하였다. 이러한 결과는 백신을 통한 두경부암의 예방이 가능함을 확인한 획기적인 성과라고 판단된다.
  • English
  • Objective: HPV is the cause of up to 60% of head and neck squamous cell cancers (HNSCCs). These HPV+ HNSCCs express viral oncoproteins. Thus we tested the vaccine targeting those antigens for prophylactic tool against HPV16 E6/E7 expressing tumors using our preclinical mouse model of HPV+ and HPV- tonsillar cancers.
    Design: Adenoviral recombinant vaccine expressing HPV16 E6/E7 (Ad5 E6/E7) was generated. Specificity and timing of E6/E7-specific cellular immune response was determined in vivo. Ad5 E6/E7 efficacy and route of administration required for clearance of HPV+ tumor cells.
    Results: We generated adenoviral recombinant vaccine expressing functional E6/E7 oncoproteins. Splenocytes from mice immunized with Ad5 E6/E7 produced an IFN-γ to cells expressing E6/E7 but not to cells lacking these oncoproteins. A time course of IFN-γ response showed that E6/E7-specific IFN-γ production is significantly increased in the first two weeks after vaccination and is substantially maintained up to 70 days. Vaccinated mice cleared E6/E7 expressing tumor 70 days after implantation. In all doses of vaccination, mice vaccinated with Ad5 E6/E7 completely cleared their E6/E7 expressing tumor cells implanted 2 weeks after either intra-tracheal or submucosal vaccination with significant E6/E7-specific IFN-γ productions.
    Conclusions: Immunization with HPV16 E6 and E7 can be an effective armamentarium for protecting host from E6/E7 expressing HNSCC via generation of potent immune response. Such a response may be beneficial when combined with traditional treatment such as chemotherapy, radiotherapy or surgery thus improving the prognosis and quality of life of patients with HPV16 associated HNSCC.
Research result report
  • Abstract
  • Objective: HPV is the cause of up to 60% of head and neck squamous cell cancers (HNSCCs). These HPV+ HNSCCs express viral oncoproteins. Thus we tested the vaccine targeting those antigens for prophylactic tool against HPV16 E6/E7 expressing tumors using our preclinical mouse model of HPV+ and HPV- tonsillar cancers.
    Design: Adenoviral recombinant vaccine expressing HPV16 E6/E7 (Ad5 E6/E7) was generated. Specificity and timing of E6/E7-specific cellular immune response was determined in vivo. Ad5 E6/E7 efficacy and route of administration required for clearance of HPV+ tumor cells.
    Results: We generated adenoviral recombinant vaccine expressing functional E6/E7 oncoproteins. Splenocytes from mice immunized with Ad5 E6/E7 produced an IFN-γ to cells expressing E6/E7 but not to cells lacking these oncoproteins. A time course of IFN-γ response showed that E6/E7-specific IFN-γ production is significantly increased in the first two weeks after vaccination and is substantially maintained up to 70 days. Vaccinated mice cleared E6/E7 expressing tumor 70 days after implantation. In all doses of vaccination, mice vaccinated with Ad5 E6/E7 completely cleared their E6/E7 expressing tumor cells implanted 2 weeks after either intra-tracheal or submucosal vaccination with significant E6/E7-specific IFN-γ productions.
    Conclusions: Immunization with HPV16 E6 and E7 can be an effective armamentarium for protecting host from E6/E7 expressing HNSCC via generation of potent immune response. Such a response may be beneficial when combined with traditional treatment such as chemotherapy, radiotherapy or surgery thus improving the prognosis and quality of life of patients with HPV16 associated HNSCC.
  • Research result and Utilization method
  • HPV E6, E7 암단백질이 편평 편평상피암을 포함한 두경부암의 발생에 주요한 역할을 하며 이에 대한 immunotherapy가 HNSCC를 예방할 수 있음을 확인하였슴.또한 그 기전에는 세포매개성 면역반응이 주요한 역할을 담당함을 증명하였슴.
    이 결과는 HPV E6, E7에 대한 immunotherapy가 HNSCC의 예방에 탁월한 효과가 있슴을 시사하며 이를 이용한 백신의 개발은 실제 임상에서 두경부암 환자의 치료에 크게 기여할 것으로 생각되며 사회적 경제적으로 획기적인 우수성이 있다고 사료됨.
  • Index terms
  • HPV, HNSCC, immune response
  • List of digital content of this reports
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