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Bispecific anti-CD3 x anti-B7-H3 antibody mediates T cell cytotoxic ability to human melanoma in vitro and in vivo

  • Juan MaEmail author
  • Tengfei Shang
  • Pan Ma
  • Xin Sun
  • Jin Zhao
  • Ximing Sun
  • Man ZhangEmail author
PRECLINICAL STUDIES
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Summary

Inhibition of the B7-H3 immune checkpoint is reported to limit the tumor growth of B7-H3+ tumors. In this study, we demonstrated B7-H3 expression in human melanoma cells, including a primary culture and several cell lines. Furthermore, we investigated whether B7-H3 could serve as a target for T cell-mediated immunotherapy against melanoma. The cytotoxic capacity of activated T cells (ATCs) armed with an anti-CD3 x anti-B7-H3 bispecific antibody (B7-H3Bi-Ab) to melanoma cells was measured using a bioluminescent signal through a luciferase reporter on tumor cells. In contrast to unarmed ATCs, B7-H3Bi-Ab-armed ATCs exhibited increased cytotoxicity against melanoma cells at effector/target ratios from 1:1 to 20:1. Moreover, B7-H3Bi-Ab-armed ATCs secreted more interferin-gamma (IFN-γ), accompanied by higher levels of activating marker CD69 and CD25 expression. Infusion of B7-H3Bi-Ab-armed ATCs suppressed melanoma growth in a xenograft mouse model. Taken together, our results indicate that B7-H3Bi-Ab-armed ATCs may be a promising approach to immunotherapy for melanoma patients.

Keywords

Melanoma B7-H3 Bispecific antibody Immunotherapy 

Notes

Funding

This work is funded by grants from the National Nature Science Foundation of China (No.31400754) and Beijing Municipal Administration of Hospitals’ Ascent Plan (DFL20150701).

Compliance with ethical standards

Conflicts of interest

Juan Ma, Tengfei Shang, Pan Ma, Xin Sun, Jin Zhao, Ximing Sun, and Man Zhang declare that they have no conflicts of interest.

Ethical approval

All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee. The animal study complied with the Guide for the Care and Use of Laboratory Animals of the Ministry of Health, and the protocol was approved by the Ethics Committee of Beijing Shijitan Hospital of Capital Medical University.

Informed consent

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

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Clinical Laboratory Medicine, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
  2. 2.Clinical Laboratory MedicinePeking University Ninth School of Clinical MedicineBeijingChina
  3. 3.Beijing Key Laboratory of Urinary Cellular Molecular DiagnosticsBeijingChina
  4. 4.Medical Experimental CentreChina Academy of Chinese Medical SciencesBeijingChina
  5. 5.Key Laboratory of Protein and Peptide Pharmaceuticals, Institute of BiophysicsChinese Academy of SciencesBeijingChina

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