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PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein

Author

Listed:
  • Min Thura

    (Agency for Science, Technology and Research (A*STAR))

  • Abdul Qader Al-Aidaroos

    (Agency for Science, Technology and Research (A*STAR))

  • Abhishek Gupta

    (Agency for Science, Technology and Research (A*STAR))

  • Cheng Ean Chee

    (National University Cancer Institute, Singapore (NCIS))

  • Soo Chin Lee

    (National University Cancer Institute, Singapore (NCIS))

  • Kam Man Hui

    (National Cancer Centre Singapore)

  • Jie Li

    (Agency for Science, Technology and Research (A*STAR))

  • Yeoh Khay Guan

    (National University of Singapore)

  • Wei Peng Yong

    (National University Cancer Institute, Singapore (NCIS))

  • Jimmy So

    (National University Cancer Institute, Singapore (NCIS))

  • Wee Joo Chng

    (National University Cancer Institute, Singapore (NCIS))

  • Chin Hin Ng

    (National University Cancer Institute, Singapore (NCIS))

  • Jianbiao Zhou

    (National University Cancer Institute, Singapore (NCIS))

  • Ling Zhi Wang

    (National University of Singapore)

  • John Shyi Peng Yuen

    (Singapore General Hospital)

  • Henry Sun Sien Ho

    (Singapore General Hospital)

  • Sim Mei Yi

    (Singapore General Hospital)

  • Edmund Chiong

    (National University Cancer Institute, Singapore (NCIS))

  • Su Pin Choo

    (National Cancer Centre Singapore)

  • Joanne Ngeow

    (Agency for Science, Technology and Research (A*STAR)
    National Cancer Centre Singapore
    Nanyang Technological University)

  • Matthew Chau Hsien Ng

    (National Cancer Centre Singapore)

  • Clarinda Chua

    (National Cancer Centre Singapore)

  • Eugene Shen Ann Yeo

    (Singapore General Hospital)

  • Iain Bee Huat Tan

    (National Cancer Centre Singapore)

  • Joel Xuan En Sng

    (Agency for Science, Technology and Research (A*STAR))

  • Nicholas Yan Zhi Tan

    (Agency for Science, Technology and Research (A*STAR))

  • Jean Paul Thiery

    (Agency for Science, Technology and Research (A*STAR))

  • Boon Cher Goh

    (National University Cancer Institute, Singapore (NCIS))

  • Qi Zeng

    (Agency for Science, Technology and Research (A*STAR)
    National University of Singapore)

Abstract

Tumor-specific antibody drugs can serve as cancer therapy with minimal side effects. A humanized antibody, PRL3-zumab, specifically binds to an intracellular oncogenic phosphatase PRL3, which is frequently expressed in several cancers. Here we show that PRL3-zumab specifically inhibits PRL3+ cancer cells in vivo, but not in vitro. PRL3 antigens are detected on the cell surface and outer exosomal membranes, implying an ‘inside-out’ externalization of PRL3. PRL3-zumab binds to surface PRL3 in a manner consistent with that in classical antibody-dependent cell-mediated cytotoxicity or antibody-dependent cellular phagocytosis tumor elimination pathways, as PRL3-zumab requires an intact Fc region and host FcγII/III receptor engagement to recruit B cells, NK cells and macrophages to PRL3+ tumor microenvironments. PRL3 is overexpressed in 80.6% of 151 fresh-frozen tumor samples across 11 common cancers examined, but not in patient-matched normal tissues, thereby implicating PRL3 as a tumor-associated antigen. Targeting externalized PRL3 antigens with PRL3-zumab may represent a feasible approach for anti-tumor immunotherapy.

Suggested Citation

  • Min Thura & Abdul Qader Al-Aidaroos & Abhishek Gupta & Cheng Ean Chee & Soo Chin Lee & Kam Man Hui & Jie Li & Yeoh Khay Guan & Wei Peng Yong & Jimmy So & Wee Joo Chng & Chin Hin Ng & Jianbiao Zhou & L, 2019. "PRL3-zumab as an immunotherapy to inhibit tumors expressing PRL3 oncoprotein," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10127-x
    DOI: 10.1038/s41467-019-10127-x
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