ArticleJournal for immunotherapy of cancer2024
Antigen-independent activation is critical for the durable antitumor effect of GUCY2C-targeted CAR-T cells.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Mechanism of neoantigen generation and advances in neoantigen-based immunotherapies in colorectal cancer.Medical oncology (Northwood, London, England) · 2026Review
- Guanylyl Cyclase 2C-Targeted Chimeric Antigen Receptor T-Cell Therapy in Patients With Metastatic Colorectal Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2026Article
- In-Use Stability and Device Compatibility Define Clinically Actionable Handling Limits for a GMP-Produced AttenuatedVaccines · 2026Article
- 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
- Optimizing CAR T cell therapy for solid tumours: a clinical perspective.Nature reviews. Clinical oncology · 2025Review
- A Tonic Signaling Code Predicts CAR-T Cell Efficacy in Diffuse Midline Glioma.bioRxiv : the preprint server for biology · 2025Article
- MARC, a novel modular chimeric antigen receptor, improves T cell-based cancer immunotherapies by preventing early T cell exhaustion and enhancing persistence.Journal for immunotherapy of cancer · 2025Article
- Framework humanization enhances GM3(Neu5Gc)-targeting CAR-T cell function by reducing tonic signaling.Frontiers in immunology · 2025Article
- Inflammation-associated drug resistance and tumor growth in TNBC.Frontiers in immunology · 2025Review
- Prospects of engineered bacteria-assisted CAR T Cell therapy in gastrointestinal cancers.Oncology reviews · 2025Review
- Isolation of Novel Fully Human Single-Domain Antibodies Targeting GUCY2C from a Heavy-Chain-Only Transgenic Mouse Platform.Technology in cancer research & treatmentArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundChimeric antigen receptor (CAR)-T cells face many obstacles in solid tumor therapy, including heterogeneous antigen expression and inefficient T cell persistence. Guanylyl cyclase C (GUCY2C) has been identified as a suitable tumor antigen for targeted therapy due to its intestinal-restricted expression pattern in normal tissues and steady overexpression in gastrointestinal tumors, especially colorectal cancer. An antigen-sensitive and long-lasting CAR-T cell targeting GUCY2C was investigated in this study.
methodsUsing constructed tumor cell lines with various GUCY2C expression densities, we screened out an antigen-sensitive single chain variable fragment (scFv) that enabled CAR-T cells to efficiently eradicate the GUCY2C lowly expressed tumor cells. CAR-T cells with different compositions of the hinge, transmembrane and costimulatory domains were also constructed for selection of the long-lasting CAR-T format with durable antitumor efficacy in vitro and in tumor-bearing mice. The underlying mechanism was further investigated based on mutation of the hinge and transmembrane domains.
resultsWe found that the composition of the antigen-sensitive scFv, CD8α hinge, CD8α transmembrane, and CD28 costimulatory domains boosted CAR-T cells to rapidly kill tumors, maintain high expansion capacity, and long-term efficacy in various colorectal cancer models. The durable antitumor function was attributed to the optimal CAR tonic signaling that conferred CAR-T cells with autonomous activation, proliferation, survival and cytokine release in the absence of antigen stimulation. The tonic signaling was associated with the length and the cysteine residues in the CD8α hinge and transmembrane domains.
conclusionsThis study demonstrated a potent GUCY2C-targeted CAR-T cell for gastrointestinal tumor therapy and highlights the importance of adequate tonic signaling for effective CAR-T cell therapy against solid tumors.
Indexed as
Identifiers
What OpenQuestion holds
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.