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Published in: Cancer Immunology, Immunotherapy 10/2023

07-07-2023 | Breast Cancer | Research

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

Authors: Peiwei Yang, Fan Yu, Zheng Yao, Xu Ding, Hanmei Xu, Juan Zhang

Published in: Cancer Immunology, Immunotherapy | Issue 10/2023

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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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Literature
7.
go back to reference Jabbarzadeh Kaboli P et al (2022) Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates. Am J Cancer Res 12(4):1671–1685PubMedPubMedCentral Jabbarzadeh Kaboli P et al (2022) Shedding light on triple-negative breast cancer with Trop2-targeted antibody-drug conjugates. Am J Cancer Res 12(4):1671–1685PubMedPubMedCentral
8.
go back to reference Kristiansen G et al (2003) CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9(13):4906–4913PubMed Kristiansen G et al (2003) CD24 expression is a new prognostic marker in breast cancer. Clin Cancer Res 9(13):4906–4913PubMed
9.
go back to reference Pirruccello SJ, LeBien TW (1986) The human B cell-associated antigen CD24 is a single chain sialoglycoprotein. J Immunol (Baltimore, md.: 1950) 136(10):3779–3784CrossRef Pirruccello SJ, LeBien TW (1986) The human B cell-associated antigen CD24 is a single chain sialoglycoprotein. J Immunol (Baltimore, md.: 1950) 136(10):3779–3784CrossRef
18.
go back to reference Sun F et al (2021) Bispecific CAR-T cells targeting both BCMA and CD24: a potentially treatment approach for multiple myeloma. Blood 138:2802CrossRef Sun F et al (2021) Bispecific CAR-T cells targeting both BCMA and CD24: a potentially treatment approach for multiple myeloma. Blood 138:2802CrossRef
27.
go back to reference Yamashita N et al (2021) MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor. J Immunother Cancer 9:1CrossRef Yamashita N et al (2021) MUC1-C integrates activation of the IFN-γ pathway with suppression of the tumor. J Immunother Cancer 9:1CrossRef
28.
go back to reference Wei J et al (2018) A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects. Cell Immunol 331:49–58CrossRefPubMed Wei J et al (2018) A novel AXL chimeric antigen receptor endows T cells with anti-tumor effects. Cell Immunol 331:49–58CrossRefPubMed
29.
go back to reference Chen H et al (2021) CD27 enhances the killing effect of CAR T cells targeting trophoblast cell. Cancer Immunol Immunother 70:2059–2071CrossRefPubMed Chen H et al (2021) CD27 enhances the killing effect of CAR T cells targeting trophoblast cell. Cancer Immunol Immunother 70:2059–2071CrossRefPubMed
Metadata
Title
CD24 is a novel target of chimeric antigen receptor T cells for the treatment of triple negative breast cancer
Authors
Peiwei Yang
Fan Yu
Zheng Yao
Xu Ding
Hanmei Xu
Juan Zhang
Publication date
07-07-2023
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 10/2023
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-023-03491-7

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