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The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer

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Summary

Expression of CD155 differs between tumor and normal tissues, and high expression of this molecule can promote tumor metastasis. Here, we investigate whether CD155 can serve as a target for T cell-mediated immunotherapy of human prostate cancer. We first demonstrate that prostate cancer cells, including PC-3, PC-3 M, and LNCAP cells, express CD155 at high levels. Next, the specific cytotoxic activity of activated T cells (ATCs) armed with a novel anti-CD3 × anti-CD155 bispecific antibody (CD155Bi-Ab) against tumor cells was evaluated by flow cytometry, lactate dehydrogenase assay (LDH), and ELISA. In contrast to unarmed ATCs, an increase in the cytotoxic activity of CD155Bi-armed ATCs against tumor cells was observed at an effector/target (E/T) ratio of 5:1. Moreover, CD155Bi-armed ATCs secreted more IFN-γ, TNF-α, and IL-2 and expressed higher levels of the activation marker CD69 than did unarmed ATCs. As CD155 Bi-Ab enhances the ability of ATCs to kill prostate cancer cells, CD155 is an effective target for cytotoxic T cells in human prostate cancer therapy.

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Funding

The work was supported by the National Key R&D Plan (2016YFC1000702) and the Beijing Natural Science Foundation (7172106).

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Authors and Affiliations

  1. Department of Clinical Laboratory, Beijing Shijitan Hospital, Capital Medical University, 10 Tieyi Road, Haidian District, Beijing, 100038, China

    Huijun Zhao, Juan Ma, Ting Lei & Man Zhang

  2. Beijing Key Laboratory of Urinary Cellular Molecular Diagnostics, Beijing, 100038, China

    Huijun Zhao, Juan Ma, Ting Lei, Wanru Ma & Man Zhang

  3. Department of Clinical Laboratory, Peking University Ninth School of Clinical Medicine, Beijing, 100038, China

    Ting Lei & Man Zhang

Authors
  1. Huijun Zhao
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  2. Juan Ma
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  3. Ting Lei
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  4. Wanru Ma
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  5. Man Zhang
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Corresponding author

Correspondence to Man Zhang.

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Conflicts of interest

Huijun Zhao, Juan Ma, Ting Lei, Wanru Ma, Man Zhang declare that they have no conflicts of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This article does not contain any studies with animals performed by any of the authors.

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Informed consent was obtained from all individual participants included in the study.

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Zhao, H., Ma, J., Lei, T. et al. The bispecific anti-CD3 × anti-CD155 antibody mediates T cell immunotherapy for human prostate cancer. Invest New Drugs 37, 810–817 (2019). https://doi.org/10.1007/s10637-018-0683-9

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  • DOI: https://doi.org/10.1007/s10637-018-0683-9

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