Breakthrough in CAR T-Cell Therapy for Gastrointestinal Cancers

Strategic Insights -

Researchers at Fudan University have made a significant discovery in the field of immunotherapy, utilizing a novel approach to target and eliminate gastrointestinal cancer (GIC) cells. The study, published in Cancer Immunology Research, employed a Sequentially Tumor-selected Antibody and Antigen Retrieval (STAR) system to isolate a nanobody that directs CAR T cells to attack GI tumor cells in preclinical mouse models.

Key Takeaways:

  • The researchers identified a nanobody, VHHB30, that specifically binds to the N-terminal domain of carcinoembryonic antigen (CEA), a protein commonly expressed in GICs.
  • The resulting VHHB30-CAR T cells (CEACARTs) exhibited cytotoxicity against both colorectal and gastric cancer cell lines in vitro in a CEA-dependent manner.
  • Third-generation CEACARTs showed enhanced antitumor activity compared to second-generation CEACARTs.
  • In vivo studies demonstrated that CEACARTs eradicated various colorectal and gastric tumor xenografts in preclinical mouse models.
  • The study suggests a promising approach for CAR T-cell therapy development in GICs through unbiased in vivo selection of potent VHH binders.

Statistics:

  • 15-20% of all cancer deaths are attributed to GICs, including gastric cancers (GCs) and colorectal cancers (CRCs).
  • The study involved the use of preclinical mouse models to evaluate the efficacy of CEACARTs in eliminating GIC cells.
  • The CAR T-cell therapy approach has shown significant promise in treating leukemia, with improvements in survival rates and reduced toxicity.
  • The research has the potential to lead to the development of more effective treatments for GICs, reducing the high mortality rates associated with these cancers.

Sources:

  • "Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts." Cancer Immunology Research, 2025.
  • "Adoptive T-cell immunotherapy, especially with T cells expressing chimeric antigen receptors (CAR) targeting CD19, has revolutionized leukemia treatment." Fudan University, Shanghai, People's Republic of China.
  • Cancer Immunology Research can be contacted at: Amer Assoc Cancer Research, 615 Chestnut St, 17TH Floor, Philadelphia, PA 19106-4404, USA.
  • NewsRx. Fudan University Reports Findings in Xenografts (Nanobody-Directed CEA-targeting CAR T Cells Eliminate Gastrointestinal Cancer Xenografts). Nanotechnology Weekly. June 9, 2025; p 429.