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
  • 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. [email protected].
  • 8. Department of Human Cell Biology and Genetics, School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China. [email protected].
  • 9. Cancer Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing, PR China. [email protected].
  • 10. School of Medicine, Southern University of Science and Technology, Shenzhen, Guangdong, PR China. [email protected].
  • # 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.

Products