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Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy

Cancer Immunology, Immunotherapy volume 70, pages 2795–2803 (2021)Cite this article

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Abstract

CD133 + cancer stem cells mediate chemoresistance in multiple aggressive cancers, and anti-CD133 chimeric antigen receptor T (CAR-T) cells are designed to selectively target cisplatin-resistant gastric cancer stem cells in this investigation. The relative CD133 expression was detected in gastric cancer patients before and after cisplatin treatment. Anti-CD133 CAR-T cells were incubated with cisplatin-exposed CD133+ BGC-823 cells to evaluate the killing efficacy. At the same time, the canonical T cell activation markers were assayed by fluorescence-activated cell sorting, and the functional cytokine profile was detected with enzyme-linked immunosorbent assays. In addition to the percentage of CD133 positive stem cell-like cells, the volume and weight of subcutaneous tumors in BGC-823, KATO III and MKN-28 xenograft models were measured to evaluate the anti-tumor activity of cisplatin and anti-CD133 CAR-T combination strategy. After cisplatin treatment, both human samples and BGC-823 cells showed up-regulated CD133 expression. Anti-CD133 CAR-T cells exhibited pronounced killing efficiency against cisplatin-exposed CD133+ BGC-823 cells with up-regulated activation markers and cytotoxicity cytokine production. Moreover, cisplatin and anti-CD133 CAR-T combination treatment inhibited tumor progression in three different xenograft models with diminished CD133 positive stem cell-like cell infiltration. These results indicate that cisplatin and anti-CD133 CAR-T combination strategy can simultaneously target normal and stem cell-like gastric cancer cells to improve the treatment outcome.

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Data will be made available upon reasonable request.

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  • 09 December 2021

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Acknowledgment

This work was supported by Shanghai Anticancer Association “Aoxiang” Project (SACA-AX201901).

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Author notes

  1. Yang Han and Bo Sun these authors contributed equally to this work.

Authors and Affiliations

  1. Department of Gastric Surgery, Fudan University Shanghai Cancer Center, No. 270 Dongan Road, Xuhui, 200032, Shanghai, China

    Yang Han, Bo Sun, Hong Cai & Yi Xuan

  2. Department of Oncology, Shanghai Medical College, Fudan University, No. 270 Dongan Road, Xuhui, 200032, Shanghai, China

    Yang Han, Bo Sun, Hong Cai & Yi Xuan

Authors
  1. Yang Han
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  2. Bo Sun
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  3. Hong Cai
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  4. Yi Xuan
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Correspondence to Hong Cai or Yi Xuan.

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Han, Y., Sun, B., Cai, H. et al. Simultaneously target of normal and stem cells-like gastric cancer cells via cisplatin and anti-CD133 CAR-T combination therapy. Cancer Immunol Immunother 70, 2795–2803 (2021). https://doi.org/10.1007/s00262-021-02891-x

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  • DOI: https://doi.org/10.1007/s00262-021-02891-x

Keywords

  • Cisplatin
  • CAR-T
  • CD133
  • Gastric cancer