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

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

  • Br J Cancer. 2025 Jul 28. doi: 10.1038/s41416-025-03114-1.
Yuling Sheng # 1,  Li Yan # 2,  Qi Liu 1,  Yifan Peng 3,  Jingyun Tan 4,  Wenhua Li 4,  Wei Mao 4,  Wenqing Wei 4,  Yanyun Chang 5,  Linlin Cao 6,  Yi Tan 1,  Yanlin Xiao 1,  Wenyong Zhang 1,  Jing Gao 7,  Yang Xu 8,  Changzheng Du 9 10
Affiliations

Affiliations

  • 1 Key University Laboratory of Metabolism and Health of Guangdong, Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
  • 2 Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China.
  • 3 Department of Unit III & Ostomy Service, Gastrointestinal Cancer Center, Beijing Cancer Hospital & Institute, Beijing, PR China.
  • 4 Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, PR China.
  • 5 Cancer Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, PR China.
  • 6 Peking University People's Hospital, Beijing, PR China.
  • 7 Department of Oncology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, PR China. gaojing_pumc@163.com.
  • 8 Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China. xuy6@sustech.edu.cn.
  • 9 Cancer Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, PR China. dzza04606@btch.edu.cn.
  • 10 School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China. dzza04606@btch.edu.cn.
  • # Contributed equally.
PMID: 40721524 DOI: 10.1038/s41416-025-03114-1
Abstract

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.

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