Evidence map›Paper›PMID 39315411›Full record

ArticleCancer biology & therapy2024

CD8α Structural Domains Enhance GUCY2C CAR-T Cell Efficacy.

Trevor R Baybutt, Ariana A Entezari, Adi Caspi, Ross E Staudt, Robert D Carlson, Scott A Waldman, Adam E Snook

Abstract read
In one paragraph

Article in Cancer biology & therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing 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

9 citing papers in PubMed.

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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

7 authors.

Trevor R BaybuttDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-5951-5875
Ariana A EntezariDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-7878-3170
Adi CaspiDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0002-1917-6298
Ross E StaudtDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0003-1439-7937
Robert D CarlsonDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-7770-6894
Scott A WaldmanDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-6619-175X
Adam E SnookDepartment of Pharmacology, Physiology, and Cancer Biology, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, USA.ORCID 0000-0001-9216-4560

Funding

X-Ray Crystallography and Macromolecular CharacterizationP30CA056036 · NCI · THOMAS JEFFERSON UNIVERSITY · PI Andrew Chapman · 1995 to 2026
$94.8M
Alcohol Tissue InjuryT32AA007463 · NIAAA · THOMAS JEFFERSON UNIVERSITY · PI HOEK, JOANNES B, VADIGEPALLI, RAJANIKANTH · 1985 to 2021
$9.1M
Targeting visceral pain through intestinal neuropod cell GUCY2C signalingR01DK138834 · NIDDK · THOMAS JEFFERSON UNIVERSITY · PI MANUEL L COVARRUBIAS, Scott A. Waldman · 2023 to 2026
$3.4M
(PQ1) GUCY2C hormone loss translates APC-Beta-catenin mutations into epithelial transformationR01CA206026 · NCI · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2016 to 2020
$1.8M
Training Program in Cancer BiologyT32CA236736 · NCI · THOMAS JEFFERSON UNIVERSITY · PI APLIN, ANDREW ERIC, LANGUINO, LUCIA R. · 2019 to 2023
$1.1M
Neuroprotection by the GUCY2C gut-brain axis in Parkinson's diseaseR21NS130388 · NINDS · THOMAS JEFFERSON UNIVERSITY · PI WALDMAN, SCOTT A · 2023 to 2023
$429k
Off-the-shelf CAR-T Therapy via Tumor-Selective Immuno-engagersR21CA267087 · NCI · LEHIGH UNIVERSITY · PI SNOOK, ADAM, THEVENIN, DAMIEN · 2022 to 2023
$402k
Ligand-Induced Recruitment of CAR-T Cells to Colorectal CancersR21CA286339 · NCI · THOMAS JEFFERSON UNIVERSITY · PI KIM, SANGWON VINCENT, SNOOK, ADAM · 2024 to 2025
$401k
NCI NIH HHS P30 CA056036NCI NIH HHS R01 CA206026NCI NIH HHS R21 CA267087NCI NIH HHS R21 CA286339NCI NIH HHS T32 CA236736NIAAA NIH HHS T32 AA007463NIDDK NIH HHS R01 DK138834NINDS NIH HHS R21 NS130388
6 · The paper itself

Abstract

Despite success in treating some hematological malignancies, CAR-T cells have not yet produced similar outcomes in solid tumors due, in part, to the tumor microenvironment, poor persistence, and a paucity of suitable target antigens. Importantly, the impact of the CAR components on these challenges remains focused on the intracellular signaling and antigen-binding domains. In contrast, the flexible hinge and transmembrane domains have been commoditized and are the least studied components of the CAR. Here, we compared the hinge and transmembrane domains derived from either the CD8ɑ or CD28 molecule in identical GUCY2C-targeted third-generation designs for colorectal cancer. While these structural domains do not contribute to differences in antigen-independent contexts, such as CAR expression and differentiation and exhaustion phenotypes, the CD8ɑ structural domain CAR has a greater affinity for GUCY2C. This results in increased production of inflammatory cytokines and granzyme B, improved cytolytic effector function with low antigen-expressing tumor cells, and robust anti-tumor efficacy

Indexed as

CD8 AntigensAnimalsCell Line, TumorColorectal NeoplasmsHumansImmunotherapy, AdoptiveMiceReceptors, Chimeric AntigenReceptors, EnterotoxinCD8 antigen, alpha chainCD8 AntigensGUCY2C protein, humanReceptors, Chimeric AntigenReceptors, EnterotoxinCAR-T cell therapyChimeric antigen receptorcolorectal cancerGUCY2C

Identifiers

PMID39315411
PMCPMC11423665

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Registered trials

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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.