Evidence map›Paper›PMID 41005308›Full record

ArticleCell2025

Safe immunosuppression-resistant pan-cancer immunotherapeutics by velcro-like density-dependent targeting of tumor-associated carbohydrate antigens.

Raymond W Zhou, Paresh Kumar Purohit, Jai Hyun Kim, Sung-Uk Lee, Nicole Burshteyn, Delia Tifrea, Andres Cordon, Ani Grigorian, Barbara L Newton, Robert A Edwards and 1 more

Abstract read
In one paragraph

Article in Cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed, 1 pooled it
–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

12 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Spatial Glyco-Codes Define Human Liver Pathology and Progression.bioRxiv : the preprint server for biology · 2026
    Article
  6. Review
  7. DHX37 and tumor growth: a novel avenue for melanoma research.Journal of translational medicine · 2026
    Article
  8. Double trouble for the tumour glycocode.Nature reviews. Cancer · 2026
    Article
  9. Article
  10. The Five-Decade Journey of Small Cell Lung Cancer.Cancer communications (London, England) · 2026
    Review
  11. Review
  12. 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

11 authors.

Raymond W ZhouDepartment of Neurology, University of California, Irvine, Irvine, CA, USA; GlyTR Therapeutics Inc., Irvine, CA, USA.
Paresh Kumar PurohitDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Jai Hyun KimDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Sung-Uk LeeDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Nicole BurshteynDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Delia TifreaDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.
Andres CordonDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Ani GrigorianDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Barbara L NewtonDepartment of Neurology, University of California, Irvine, Irvine, CA, USA.
Robert A EdwardsDepartment of Pathology & Laboratory Medicine, University of California, Irvine, Irvine, CA, USA.
Michael DemetriouDepartment of Neurology, University of California, Irvine, Irvine, CA, USA; Department of Microbiology and Molecular Genetics, University of California, Irvine, Irvine, CA, USA. Electronic address: mdemetri@uci.edu.

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Univ.of Calif., Irvine Cancer Center Support GrantP30CA062203 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI Melanie Funes · 1994 to 2026
$57.9M
Institute for Clinical and Translational ScienceUM1TR004927 · NCATS · UNIVERSITY OF CALIFORNIA-IRVINE · PI DAN M COOPER, Eric J. Vilain · 2024 to 2026
$12.2M
NRSA Training CoreTL1TR001875 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI SPANN, MARISA N, TAYLOR, JACQUELYN Y · 2016 to 2025
$8.9M
N-glycosylation and Immunotherapy for cancerU01CA233078 · NCI · UNIVERSITY OF CALIFORNIA-IRVINE · PI DEMETRIOU, MICHAEL · 2018 to 2022
$3.4M
Extended half-life GlyTR1 combined with checkpoint blockade for Cancer ImmunotherapyR42CA285234 · NCI · GLYTR THERAPEUTICS, INC. · PI DEMETRIOU, MICHAEL, ZHOU, RAYMOND WENHOU · 2023 to 2025
$2.4M
Cancer Immunotherapy Targeting Tn AntigenR41CA261408 · NCI · GLYTR THERAPEUTICS, INC. · PI DEMETRIOU, MICHAEL, ZHOU, RAYMOND WENHOU · 2021 to 2021
$398k
O-Glycan-dependent Immunotherapy for CancerR41CA233111 · NCI · GLYTR THERAPEUTICS, INC. · PI DEMETRIOU, MICHAEL · 2018 to 2019
$301k
NCATS NIH HHS TL1 TR001875NCATS NIH HHS UL1 TR001873NCATS NIH HHS UM1 TR004927NCI NIH HHS P30 CA062203NCI NIH HHS R41 CA233111NCI NIH HHS R41 CA261408NCI NIH HHS R42 CA285234NCI NIH HHS U01 CA233078
6 · The paper itself

Abstract

Bispecific antibodies and chimeric antigen receptor T cells are some of the most potent cancer immunotherapeutics in clinical use, yet most cancers remain poorly targetable. High-affinity antibodies required to maximize killing detect low antigen expression in normal tissue, risking "on-target, off-cancer" toxicity. This compels identification of cancer-restricted cell-surface protein antigens, which are rare. Tumor-associated carbohydrate antigens (TACAs) are the most abundant and widespread cancer antigens known but are poorly targetable by antibodies. Here, we describe glycan-dependent T cell recruiter (GlyTR) pan-cancer immunotherapeutics that utilize high-avidity "velcro-like" lectin binding to kill cells with high but not low TACA expression. GlyTR1 and GlyTR2 bind immunosuppressive β1,6GlcNAc-branched N-glycans or multiple TACAs (Tn, sialyl-Tn, LacDiNAc, and GD2), respectively, overcome immunosuppressive mechanisms in the tumor microenvironment and trigger target-density-dependent T cell-mediated pan-cancer killing, yet they lack toxicity in mice with human-like TACA expression. Density-dependent lectin binding to TACAs provides highly potent and safe pan-cancer immunotherapeutics.

Indexed as

Antigens, Tumor-Associated, CarbohydrateImmunotherapyNeoplasmsAnimalsCell Line, TumorFemaleHumansImmunosuppression TherapyLectinsMicePolysaccharidesT-LymphocytesTumor MicroenvironmentAntigens, Tumor-Associated, CarbohydrateLectinsPolysaccharidesbispecificglycan-dependent T cell recruiterimmunosuppressionimmunotherapypan-cancersiayl-Tn antigenTn antigentumor-associated carbohydrate antigenstumor microenvironmentβ1,6GlcNAc-branched N-glycans

Identifiers

PMID41005308
PMCPMC12767472

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.