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The Korean Association of Immunobiologists (대한면역학회)
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Enhanced CEA-specific Immune Responses by Tat-LLO Fusion Protein

Tat-LLO 융합 단백질에 의한 CEA 특이 항종양 면역 반응의 증가

  • Yi, Soon-Aei (Department of Microbiology and Immunology, The Catholic University of Korea) ;
  • Sohn, Hyun-Jung (Department of Microbiology and Immunology, The Catholic University of Korea) ;
  • Kim, Chang-Hyun (Department of Microbiology and Immunology, The Catholic University of Korea) ;
  • Park, Mi-Young (Department of Microbiology and Immunology, The Catholic University of Korea) ;
  • Oh, Seong-Taek (Department of Surgery, College of Medicine, The Catholic University of Korea) ;
  • Kim, Tai-Gyu (Department of Microbiology and Immunology, The Catholic University of Korea)
  • 이순애 (가톨릭대학교 의과대학 미생물학교실) ;
  • 손현정 (가톨릭대학교 의과대학 미생물학교실) ;
  • 김창현 (가톨릭대학교 의과대학 미생물학교실) ;
  • 박미영 (가톨릭대학교 의과대학 미생물학교실) ;
  • 오승택 (가톨릭대학교 의과대학 외과학교실) ;
  • 김태규 (가톨릭대학교 의과대학 미생물학교실)
  • Published : 2005.09.30
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Abstract

Background: Carcinoembryonic antigen (CEA) is well-known soluble tumor marker frequently detectable in peripheral blood of carcinoma patients and considered as good target for antigen-specific immunotherapy. However, it is known that the induction of immune response to CEA is very difficult because CEA is a self-antigen expressed in fetal cells and weakly expressed in normal colorectal epithelial cells. To enhance anti-tumor immunity specific for CEA, recombinant CEA protein was modified using listeriolysin O (LLO) for endosomal lysis and trans activator of transcription (Tat) domain for transducing extracellular proteins into cytoplasm. Methods: After immunization using dendritic cells pulsed with Tat-CEA, both Tat-CEA and LLO, and both Tat-CEA and Tat-LLO, antibody titer to CEA and LLO, cytotoxic T lymphocyte activity and the frequency of IFN-${\gamma}$ producing T lymphocytes were measured. Results: Immunization using DC pulsed with both Tat-CEA and Tat-LLO protein showed the increasement of production of CEA-specific antibody in serum, cytotoxic T lymphocyte activity, the frequency of IFN-${\gamma}$ secreting T cells, compared with DC pulsed with both Tat-CEA and LLO. Furthermore the ratio of CD8+T cell to $CD4^+$ cell among CEA-specific T cells was increased in group pulsed with both Tat-CEA and Tat-LLO. Conclusion: These results suggested that DC vaccine using Tat-LLO could be used for the development of effective immunotherapy for the treatment of tumor.

Keywords

References

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