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Bispecific anti-CD3×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies

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Summary

T cells are important components in the cell-mediated antitumour response. In recent years, bispecific antibodies (Bi-Abs) have become promising treatments because of their ability to recruit T cells that kill tumours. Here, we demonstrate that CD155 is expressed in a wide range of human haematologic tumours and report on the ability of the bispecific antibody anti-CD3 x anti-CD155 (CD155Bi-Ab) to activate T cells targeting malignant haematologic cells. The specific cytolytic effect of T cells armed with CD155Bi-Ab was evaluated by quantitative luciferase assay, and the results showed that the cytolytic effect of these cells was accompanied by an increase in the level of the cell-killing mediator perforin. Moreover, compared with their unarmed T-cell counterparts, CD155Bi-Ab-armed T cells induced significant cytotoxicity in CD155-positive haematologic tumour cells, as indicated by lactate dehydrogenase assays, and these results were accompanied by increased granzyme B secretion. Furthermore, CD155Bi-Ab-armed T cells produced more T-cell-derived cytokines, including TNF-α, IFN-γ, and IL-2. In conclusion, CD155Bi-Ab enhances the ability of T cells to kill haematologic tumour cells, and therefore, CD155 may serve as a novel target for immunotherapy against haematologic malignancies.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work is funded by grants from the Key Project of Science and Technology Plan of Beijing Municipal Education Commission (Beijing Municipal Science and Technology Commission, No. KZ201910025033 and No. KZ202110025028).

Author information

Authors and Affiliations

  1. Department of Pathology, Beijing Key Laboratory of Head and Neck Molecular Diagnostic Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China

    Li Ma & Honggang Liu

  2. Department of Gynecology and Obstetrics, China-Japan Friendship Hospital, Capital Medical University, Beijing, 100029, China

    Li Ma

  3. Biomedical Innovation Center, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China

    Juan Ma

  4. Department of Clinical Laboratory Medicine, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, China

    Juan Ma & Xin Sun

  5. College of Basic Medical Science, Peking University Health Science Center, Beijing, 100191, China

    Xin Sun

Authors
  1. Li Ma
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  4. Honggang Liu
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Contributions

Ma L. and Liu H. conceived and designed the experiments. Ma L. and Sun X. prepared figure 1. Ma L. and Ma J. prepared figure 2-5. Ma L., Ma J. and Liu H. wrote the mainuscript. All authors reviewed the manuscript.

Corresponding author

Correspondence to Honggang Liu.

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

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

Conflict of interest

Li Ma, Juan Ma, Xin Sun and Honggang Liu declared that they have no conflicting interests.

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Ma, L., Ma, J., Sun, X. et al. Bispecific anti-CD3×anti-CD155 antibody mediates T-cell immunotherapy in human haematologic malignancies. Invest New Drugs 41, 522–531 (2023). https://doi.org/10.1007/s10637-023-01367-2

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