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Background <p>The application of chimeric antigen receptor (CAR)-T cells in solid tumors is hindered due to the lack of specific tumor antigen and limited clinical efficacy. Our aim is to develop and validate novel CAR-T cell therapy against metastatic colorectal cancer (CRC).</p> Methods <p>By analyzing the expression of B7-H3 in CRC tissue and cell lines using immunohistochemistry (IHC) and flow cytometry, respectively, we identified B7-H3 as a potential target in CRC. We thereby developed CAR-T cells targeting B7-H3 (B7-H3 CAR-T) and evaluated their anti-tumor activity in vitro and in vivo, using patient-derived organoids (PDOs) and xenograft (PDX) models to validate its translational potential.</p> Results <p>In our cohort of 170 CRC patients, B7-H3 was significantly upregulated in CRC tumors compared to paratumor tissue, as determined by IHC staining. When co-cultured with CRC cells or PDOs, B7-H3 CAR-T cells exhibited a dose-dependent cytotoxicity in vitro. Furthermore, B7-H3 CAR-T cells effectively controlled tumor growth and metastasis in vivo, significantly prolonging survival time for the tumor-burden mice through cytotoxic killing and potential immune regulatory effects, demonstrated in both CRC cell-based and PDX-based metastatic models.</p> Conclusions <p>These findings underscore the potential efficacy of B7-H3 CAR-T cells for treating metastatic CRC and highlight its translational value.</p> <p></p>

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The pronounced cytotoxic effects of chimeric antigen receptor T cells targeting B7-H3 in organoids and liver xenografts derived from colorectal cancer patients

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月28日

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  • Yuling Sheng,
  • Li Yan,
  • Qi Liu,
  • Yifan Peng,
  • Jingyun Tan,
  • Wenhua Li,
  • Wei Mao,
  • Wenqing Wei,
  • Yanyun Chang,
  • Linlin Cao,
  • Yi Tan,
  • Yanlin Xiao,
  • Wenyong Zhang,
  • Jing Gao,
  • Yang Xu,
  • Changzheng Du

摘要

Background

The application of chimeric antigen receptor (CAR)-T cells in solid tumors is hindered due to the lack of specific tumor antigen and limited clinical efficacy. Our aim is to develop and validate novel CAR-T cell therapy against metastatic colorectal cancer (CRC).

Methods

By analyzing the expression of B7-H3 in CRC tissue and cell lines using immunohistochemistry (IHC) and flow cytometry, respectively, we identified B7-H3 as a potential target in CRC. We thereby developed CAR-T cells targeting B7-H3 (B7-H3 CAR-T) and evaluated their anti-tumor activity in vitro and in vivo, using patient-derived organoids (PDOs) and xenograft (PDX) models to validate its translational potential.

Results

In our cohort of 170 CRC patients, B7-H3 was significantly upregulated in CRC tumors compared to paratumor tissue, as determined by IHC staining. When co-cultured with CRC cells or PDOs, B7-H3 CAR-T cells exhibited a dose-dependent cytotoxicity in vitro. Furthermore, B7-H3 CAR-T cells effectively controlled tumor growth and metastasis in vivo, significantly prolonging survival time for the tumor-burden mice through cytotoxic killing and potential immune regulatory effects, demonstrated in both CRC cell-based and PDX-based metastatic models.

Conclusions

These findings underscore the potential efficacy of B7-H3 CAR-T cells for treating metastatic CRC and highlight its translational value.