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  • [Mol Ther.] Targeting of pancreatic cancer cells and stromal cells using engineered oncolytic Salmonella typhimurium 살모넬라균의 유전자 조작을 통한 췌장암 및 기질 세포의 표적화 연구

    Hunan University, 전남의대 / Wenzhi Tan, Jin Hai Zheng*, 민정준*

  • 출처
    Mol Ther.
  • 등재일
    2022 Feb 2
  • 저널이슈번호
    30(2):662-671. doi: 10.1016/j.ymthe.2021.08.023. Epub 2021 Aug 14.
  • 내용

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    Abstract
    Pancreatic cancer is resistant to conventional therapeutic interventions, mainly due to abundant cancer stromal cells and poor immune cell infiltration. Here, we used a targeted cancer therapy approach based on attenuated Salmonella typhimurium engineered to express cytolysin A (ClyA) to target cancer stromal cells and cancer cells and treat pancreatic cancer in mice. Nude mice bearing subcutaneous or orthotopic human pancreatic cancers were treated with engineered S. typhimurium expressing ClyA. The tumor microenvironment was monitored to analyze stromal cell numbers, stromal cell marker expression, and immune cell infiltration. The attenuated bacteria accumulated and proliferated specifically in tumor tissues after intravenous injection. The bacteria secreted ClyA into the tumor microenvironment. A single dose of ClyA-expressing Salmonella markedly inhibited growth of pancreatic cancer both in subcutaneous xenograft- and orthotopic tumor-bearing nude mice. Histological analysis revealed a marked decrease in expression of stromal cell markers and increased immune cell (neutrophils and macrophages) infiltration into tumors after colonization by ClyA-expressing bacteria. ClyA-expressing S. typhimurium destroyed cancer stromal cells and cancer cells in mouse models of human pancreatic cancer. This approach provides a novel strategy for combining anticancer and anti-stromal therapy to treat pancreatic cancer.

     

     

    Affiliations

    Wenzhi Tan  1 , Mai Thi-Quynh Duong  2 , Chaohui Zuo  3 , Yeshan Qin  2 , Ying Zhang  2 , Yanxia Guo  1 , Yeongjin Hong  4 , Jin Hai Zheng  5 , Jung-Joon Min  6
    1 School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China.
    2 Institute for Molecular Imaging and Theranostics, Chonnam National University Hwasun Hospital, Jeonnam 58128, Republic of Korea.
    3 Department of Gastroduodenal and Pancreatic Surgery, Hunan Cancer Hospital, Changsha, Hunan 410013, China.
    4 Department of Microbiology, Chonnam National University Medical School, Gwangju 61469, Republic of Korea.
    5 School of Biomedical Sciences, Hunan University, Changsha, Hunan 410082, China; Institute for Molecular Imaging and Theranostics, Chonnam National University Hwasun Hospital, Jeonnam 58128, Republic of Korea. Electronic address: jhzheng@hnu.edu.cn.
    6 Institute for Molecular Imaging and Theranostics, Chonnam National University Hwasun Hospital, Jeonnam 58128, Republic of Korea; Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Jeonnam 58128, Republic of Korea. Electronic address: jjmin@jnu.ac.kr.

  • 키워드
    ClyA; bacterial cancer therapy; cancer stromal cells; cytolysin A; immune cell infiltration; pancreatic cancer.
  • 편집위원

    최근 마이크로바이옴이 연구의 관심이 되고 있는 가운데 꾸준히 박테리아를 이용한 암세포의 표적화와 항암효과에 관한 연구가 기대됩니다.

    2022-04-05 11:41:02

  • 편집위원2

    췌장암은 cancer stromal cells이 많고 immune cell infiltration이 부족하여 일반적인 치료법에 대한 저항성이 매우 높은 암종이다. 본 연구는 cytolysin A (ClyA)를 발현하는 약화된 살모넬라균을 활용하여 stromal cell을 파괴할 수 있음을 증명함으로써, 췌장암 표적치료에 대한 새로운 전략을 제시하였다.

    2022-04-05 13:55:06

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