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CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer

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Abstract

Triple negative breast cancer (TNBC) is a subtype of breast cancer with the highest degree of malignancy and the worst prognosis. The application of immunotherapy for TNBC is limited. This study was to verify the potential application of chimeric antigen receptor-T cells (CAR-T cells) targeting CD24 named as 24BBz in treatment of TNBC. 24BBz was constructed by lentivirus infection and then was co-culture with breast cancer cell lines to evaluate the activation, proliferation and cytotoxicity of engineered T cells. The anti-tumor activity of 24BBz was verified in the subcutaneous xenograft model of nude mice. We found that CD24 gene was significantly up-regulated in breast cancer (BRCA), especially in TNBC. 24BBz showed antigen-specific activation and dose-dependent cytotoxicity against CD24-positive BRCA tumor cells in vitro. Furthermore, 24BBz showed significant anti-tumor effect in CD24-positive TNBC xenografts and T cells infiltration in tumor tissues, while some T cells exhibited exhaustion. No pathological damage of major organs was found during the treatment. This study proved that CD24-specific CAR-T cells have potent anti-tumor activity and potential application value in treatment of TNBC.

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Funding

This work was supported by the Project Program of State Key Laboratory of Natural Medicines (SKLNMZZ202219), the National Natural Science Foundation (NSFC81973223), the Fundamental Research Funds for the Central Universities (2632023GR08) and the Nanjing International Industry Technology Research and Development Cooperation Project (2021SX00000435-202100880).

Author information

Author notes

  1. Peiwei Yang and Fan Yu have contributed equally to this paper.

Authors and Affiliations

  1. Antibody Engineering Laboratory, Department of Molecular Biology, School of Life Science and Technology, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Juan Zhang

  2. The Engineering Research Center of Synthetic Polypeptide Drug Discovery and Evaluation, China Pharmaceutical University, Nanjing, 210009, Jiangsu Province, People’s Republic of China

    Peiwei Yang, Fan Yu, Zheng Yao & Hanmei Xu

  3. State Key Laboratory of Natural Medicines, Ministry of Education, China Pharmaceutical University, 639 Longmian Avenue, Jiangning District, Nanjing City, 210009, Jiangsu Province, People’s Republic of China

    Peiwei Yang, Zheng Yao, Hanmei Xu & Juan Zhang

  4. Department of Oral and Maxillofacial Surgery, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, 210029, People’s Republic of China

    Xu Ding

  5. Nanjing Anji Biological Technology Co., LTD, Nanjing, 210033, People’s Republic of China

    Fan Yu

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  1. Peiwei Yang
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Contributions

YPW, YF and YZ designed and performed the experiments, analyzed the data, created the figures and wrote the paper. DX collected the blood sample. ZJ and XHM conceived the idea, supervised the project, and edited the paper. All authors carefully read and approved the paper.

Corresponding authors

Correspondence to Hanmei Xu or Juan Zhang.

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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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Animal experiments were conducted in conformity with guidelines of the China Pharmaceutical University.

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Fresh blood was obtained from healthy volunteers with the approval of the Ethics Committee of China Pharmaceutical University. Informed consent was obtained from all individual participants.

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All authors and subjects in this study concur with the publish.

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Yang, P., Yu, F., Yao, Z. et al. CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer. Cancer Immunol Immunother 72, 3191–3202 (2023). https://doi.org/10.1007/s00262-023-03491-7

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