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  • [Transl Oncol.] Multimodality Imaging of Bone Marrow-Derived Dendritic Cell Migration and Antitumor Immunity.

    경북의대 / 안수비, 이상우*, 전용현*

  • 출처
    Transl Oncol.
  • 등재일
    2017 Apr
  • 저널이슈번호
    10(2):262-270. doi: 10.1016/j.tranon.2017.01.003. Epub 2017 Feb 16.
  • 내용

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    [그림1. Luc2/NIS 유전자 이입에 의한 BMDCbiological function 조사]



    [그림2. Luc2 유전자와 NIS 유전자를 이용한 BMDC 세포 추적 영상]


    Abstract

    Here, we sought to monitor bone marrow-derived dendritic cell (BMDC) migration and antitumor effects using a multimodal reporter imaging strategy in living mice. BMDCs were transduced with retroviral vector harboring human sodium iodide symporter (hNIS, nuclear imaging reporter), firefly luc2 (optical imaging reporter), and thy1.1 (surrogate marker of NIS and luc2) genes (BMDC/NF cells). No significant differences in biological functions, including cell proliferation, antigen uptake, phenotype expression, and migration ability, were observed between BMDC and BMDC/NF cells. Combined bioluminescence imaging and I-124 positron emission tomography/computed tomography clearly revealed the migration of BMDC/NF cells to draining popliteal lymph nodes at day 7 postinjection. Interestingly, marked tumor protection was observed in mice immunized with TC-1 lysate-pulsed BMDC/NF cells. Our findings suggested that multimodal reporter gene imaging of NIS and luciferase could provide insights into the biological behaviors of dendritic cells in living organisms and could be a useful tool for the optimization of DC-based immunotherapy protocols. 

     

    Author information

    Ahn SB1, Lee SB2, Singh TD1, Cho SJ3, Kim SK1, Lee IK4, Jeong SY1, Ahn BC1, Lee J5, Lee SW6, Jeon YH7.

    Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea.

    Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea.

    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea; New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, South Korea.

    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea; Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, South Korea.

    Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, South Korea.

    Department of Nuclear Medicine, Kyungpook National University Hospital, Daegu, South Korea; Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea. Electronic address: swnmlee@knu.ac.kr.

    Leading-edge Research Center for Drug Discovery and Development for Diabetes and Metabolic Disease, Kyungpook National University Hospital, Daegu, South Korea; Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea. Electronic address: jeon9014@gmail.com. 

  • 연구소개
    생체 내에서 multimodal 리포터 이미징 기술을 사용하여 골수 유래 수지상 세포 (BMDC) 이동 및 항 종양 효과를 모니터링 하는 연구를 진행하였다. 수지상 세포의 인간 요오드화 나트륨 수송체 (hNIS, 핵의학영상 리포터유전자), 반딧불이 luc2 (광학영상 리포터 유전자) 및 thy1.1 (NIS 및 luc2의 대용 마커)를 보유하는 레트로 바이러스 벡터로 형질을 도입하여 BMDC/NF 세포를 만들었다. BMDC와 BMDC / NF 세포 사이에는 세포 증식, 항원 섭취, 표현형 발현 및 이동 능력을 포함한 생물학적 기능에서 유의한 차이가 관찰되지 않았다 (그림 1). 결합된 생물 발광 영상과 I-124의 양전자 방출 단층 촬영 / 컴퓨터 단층 촬영은 주입 후 7 일째에 림프절에서 BMDC/NF 세포의 이동을 분명히 나타냈다 (그림 2). 또한 흥미롭게도, BMDC/NF 세포로 면역화 된 마우스에서 현저한 자궁경부암 면역이 관찰되었다 (그림 3). 본 연구로부터 NIS와 루시퍼라제의 multimodal reporter 유전자 영상은 살아있는 수지상 세포의 생물학적 이동에 대한 정보를 제공 할 수 있으며 DC 기반 면역 요법의 최적화에 유용한 도구가 될 수 있다고 제안했다.
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