ArticleOncoimmunology
GUCY2C-directed CAR-T cells oppose colorectal cancer metastases without autoimmunity.
Article in Oncoimmunology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 86 citations in OpenAlex.
- Multimodal radiomics for precision management of colorectal cancer.Discover oncology · 2026Review
- Construction and Evaluation of Guanylyl Cyclase C-Specific Antibody for Noninvasive Diagnosis and Targeted Therapy of Colorectal Cancer.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2026Article
- Could GUCY2C-targeted pharmacotherapy be effective in treating colorectal cancer?Expert review of clinical pharmacology · 2026Article
- Advances in immunotherapy for colorectal cancer: overcoming resistance in mismatch repair-proficient tumors.Cancer cell international · 2026Review
- DSG2-Directed CAR-T Cells Safely and Universally Eliminate Solid Tumors.Research square · 2026Article
- Next-generation CAR-T engineering for colorectal cancer: integrating targets, tumor microenvironment barriers, and emerging strategies.Frontiers in immunology · 2026Review
- IFNγ-induced antigen loss in chimeric antigen receptor-T cell therapy.Frontiers in immunology · 2026Article
- Emerging Strategies for Targeting Angiogenesis and the Tumor Microenvironment in Gastrointestinal Malignancies: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Development of a bispecific CDH17-GUCY2C ADC bearing the ferroptosis inducer RSL3 for the treatment of colorectal cancer.Cell death discovery · 2025Article
- Chimeric Antigen Receptor-T Cells in Colorectal Cancer: Pioneering New Avenues in Solid Tumor Immunotherapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2025Review
- FDA-Approved Chimeric Antigen Receptor (CAR)-T Cell Therapy for Different Cancers-A Recent Perspective.Molecular biotechnology · 2025Review
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.Cancer biology & therapy · 2024Article
- Redefining Therapeutic Approaches in Colorectal Cancer: Targeting Molecular Pathways and Overcoming Resistance.International journal of molecular sciences · 2024Review
- Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.Journal for immunotherapy of cancer · 2024Article
- Review
- Updated Clinical Perspectives and Challenges of Chimeric Antigen Receptor-T Cell Therapy in Colorectal Cancer and Invasive Breast Cancer.Archivum immunologiae et therapiae experimentalis · 2023Review
- Systemic treatment for metastatic colorectal cancer.World journal of gastroenterology · 2023Review
- Review
- Targeting gastrointestinal cancers with chimeric antigen receptor (CAR)-T cell therapy.Cancer biology & therapy · 2022Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Adoptive T-cell therapy (ACT) is an emerging paradigm in which T cells are genetically modified to target cancer-associated antigens and eradicate tumors. However, challenges treating epithelial cancers with ACT reflect antigen targets that are not tumor-specific, permitting immune damage to normal tissues, and preclinical testing in artificial xenogeneic models, preventing prediction of toxicities in patients. In that context, mucosa-restricted antigens expressed by cancers exploit anatomical compartmentalization which shields mucosae from systemic antitumor immunity. This shielding may be amplified with ACT platforms employing antibody-based chimeric antigen receptors (CARs), which mediate MHC-independent recog-nition of antigens. GUCY2C is a cancer mucosa antigen expressed on the luminal surfaces of the intestinal mucosa in mice and humans, and universally overexpressed by colorectal tumors, suggesting its unique utility as an ACT target. T cells expressing CARs directed by a GUCY2C-specific antibody fragment recognized GUCY2C, quantified by expression of activation markers and cytokines. Further, GUCY2C CAR-T cells lysed GUCY2C-expressing, but not GUCY2C-deficient, mouse colorectal cancer cells. Moreover, GUCY2C CAR-T cells reduced tumor number and morbidity and improved survival in mice harboring GUCY2C-expressing colorectal cancer metastases. GUCY2C-directed T cell efficacy reflected CAR affinity and surface expression and was achieved without immune-mediated damage to normal tissues in syngeneic mice. These observations highlight the potential for therapeutic translation of GUCY2C-directed CAR-T cells to treat metastatic tumors, without collateral autoimmunity, in patients with metastatic colorectal cancer.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.