Evidence map›Paper›PMID 41572139›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2026

Enzymatic Remodelling of Tumour Microenvironment Enhances Anti-CEACAM5 CAR T-Cell Efficacy Against Colorectal Cancer.

Debasis Banik, Christopher J Ward, Soura Chakraborty, Ziwei Zhang, Daniel Heraghty, Prasanna Suresh, Bing Li, Shekhar Kedia, Jhuma Pramanik, Simon J Davis and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Debasis BanikYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID https://orcid.org/0000-0003-1065-991X
Christopher J WardDepartment of Pathology, University of Cambridge, Cambridge, UK.
Soura ChakrabortyDepartment of Pathology, University of Cambridge, Cambridge, UK.
Ziwei ZhangYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Daniel HeraghtyYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Prasanna SureshYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Bing LiYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Shekhar KediaYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.
Jhuma PramanikDepartment of Pathology, University of Cambridge, Cambridge, UK.
Simon J DavisRadcliffe Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK.
James P RoyMRC Toxicology Unit, University of Cambridge, Cambridge, UK.
Michael A ChapmanMRC Toxicology Unit, University of Cambridge, Cambridge, UK.
Bidesh MahataDepartment of Pathology, University of Cambridge, Cambridge, UK.
David KlenermanYusuf Hamied Department of Chemistry, University of Cambridge, Cambridge, UK.ORCID https://orcid.org/0000-0001-7116-6954

Funding

Cancer Research UK RCCFEL∖100095Cancer Research UK (CRUK) DRCCIPA∖100010HORIZON EUROPE Marie Sklodowska-Curie Actions G114341MRC Project MR/V028995/1NSF-BIO/UKRI-BBSRC BB/V006126/1
6 · The paper itself

Abstract

Chimeric antigen receptor (CAR) T-cell therapy has shown unprecedented success in haematological cancers but faces challenges in solid tumours. Although carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) is differentially expressed in many solid tumours, anti-CEACAM5 CAR T-cells are ineffective. Here, we have studied the interaction of CEACAM5 targeting primary CAR T-cells with colorectal cancer (CRC) cells using fluorescence microscopy. We found that CRC cells' glycocalyx is much thicker than that of the CAR T cell causing delayed activation. Oscillating calcium fluxes, indicative of non-sustained CAR T cell activation, are observed when CAR T cells interacted with CRC cells, which increased with increasing cell-seeding time. Significant reduction in cytotoxicity is observed on going from early to longer-seeded CRC monolayers. Imaging revealed that this effect correlated with a progressive loss of accessible CEACAM5 antigen on the CRC cell surface, possibly due to their sequestration in the intercellular junction, rendering CAR T cell engagement less effective. Local proteolytic treatment with trypsin to disrupt the CRC cell monolayer, using a micropipette, increased CEACAM5 availability, decreased glycocalyx thickness, and restored sustained CAR T cell calcium fluxes. Similar enhanced interaction is observed after treatment of CRC cell monolayer with hyaluronidase, approved for use in humans. Enzymatic treatment significantly enhanced CAR T cell-mediated cytotoxicity and increased the percentage of TNF-α-secreting CAR T cells. We observed limited availability of CEACAM5 on human colorectal cancer tissues, whereas treatment with trypsin or hyaluronidase increased accessibility. Our results reveal why CAR T cells targeting CEACAM5 are ineffective and suggest possible routes to improved therapy for CRC.

Indexed as

Carcinoembryonic AntigenColorectal NeoplasmsGPI-Linked ProteinsT-LymphocytesTumor MicroenvironmentCell Line, TumorHumansImmunotherapy, AdoptiveReceptors, Chimeric AntigenCarcinoembryonic AntigenCEACAM5 protein, humanGPI-Linked ProteinsReceptors, Chimeric AntigenCAR T cellCEACAM5CRCenzymeglycocalyx

Identifiers

PMID41572139
PMCPMC12955994

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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.