Evidence map›Paper›PMID 31672936›Full record

ArticleJCI insight2019

Multiple cancer-specific antigens are targeted by a chimeric antigen receptor on a single cancer cell.

Yanran He, Karin Schreiber, Steven P Wolf, Frank Wen, Catharina Steentoft, Jonathan Zerweck, Madeline Steiner, Preeti Sharma, H Michael Shepard, Avery Posey and 7 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 13% of its field
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

8 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Article
  6. Targeting glycans for CAR therapy: The advent of sweet CARs.Molecular therapy : the journal of the American Society of Gene Therapy · 2022
    Review
  7. Review
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 7 institutions in 3 countries.

Yanran HeCommittee on Cancer Biology, and.
Karin SchreiberDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Steven P WolfDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Frank WenDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Catharina SteentoftCopenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
Jonathan ZerweckDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Madeline SteinerDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
Preeti SharmaDepartment of Biochemistry, University of Illinois, Urbana, Illinois, USA.
H Michael ShepardBiooncology Consultants, San Diego, California, USA.
Avery PoseyDepartment of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Carl H JuneCenter for Cellular Therapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Ulla MandelCopenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
Henrik ClausenCopenhagen Center for Glycomics, University of Copenhagen, Copenhagen, Denmark.
Matthias LeisegangInstitute of Immunology, Charité - Universitätsmedizin Berlin, Campus Buch, Berlin, Germany.
Stephen C MeredithDepartment of Pathology, The University of Chicago, Chicago, Illinois, USA.
David M KranzDepartment of Biochemistry, University of Illinois, Urbana, Illinois, USA.
Hans SchreiberCommittee on Cancer Biology, and.
University of Chicago · USUniversity of Copenhagen · DKUniversity of Illinois Urbana-Champaign · USBerlin Institute of Health at Charité - Universitätsmedizin Berlin · DECarolina BioOncology Institute · USTranslational Therapeutics (United States) · USUniversity of Pennsylvania · US

Funding

PATHOBIOLOGY OF MYELOMA AND ANTI-IDIOTYPIC IMMUNITYR01CA022677 · NCI · UNIVERSITY OF CHICAGO · PI SCHREIBER, HANS · 1985 to 2024
$6.3M
IMMUNOLOGY OF UNIQUE TUMOR-SPECIFIC ANTIGENSR01CA037156 · NCI · UNIVERSITY OF CHICAGO · PI SCHREIBER, HANS · 1985 to 2017
$3.1M
Directing the metabolic fate of CAR T cellsR01CA226983 · NCI · UNIVERSITY OF PENNSYLVANIA · PI JUNE, CARL H. · 2018 to 2022
$2.1M
Engineering CARs against cancer-specific glycoproteinsR21CA238628 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KRANZ, DAVID M. · 2019 to 2020
$394k
NCI NIH HHS R01 CA022677NCI NIH HHS R01 CA037156NCI NIH HHS R01 CA226983NCI NIH HHS R21 CA238628
6 · The paper itself

Abstract

Human cancer cells were eradicated by adoptive transfer of T cells transduced with a chimeric antigen receptor (CAR) made from an antibody (237Ab) that is highly specific for the murine Tn-glycosylated podoplanin (Tn-PDPN). The objectives were to determine the specificity of these CAR-transduced T (CART) cells and the mechanism for the absence of relapse. We show that although the 237Ab bound only to cell lines expressing murine Tn-PDPN, the 237Ab-derived 237CART cells lysed multiple different human and murine cancers not predicted by the 237Ab binding. Nevertheless, the 237CART cell reactivities remained cancer specific because all recognitions were dependent on the Tn glycosylation that resulted from COSMC mutations that were not present in normal tissues. While Tn was required for the recognition by 237CART, Tn alone was not sufficient for 237CART cell activation. Activation of 237CART cells required peptide backbone recognition but tolerated substitutions of up to 5 of the 7 amino acid residues in the motif recognized by 237Ab. Together, these findings demonstrate what we believe is a new principle whereby simultaneous recognition of multiple independent Tn-glycopeptide antigens on a cancer cell makes tumor escape due to antigen loss unlikely.

Indexed as

Adoptive TransferAnimalsAntigens, NeoplasmAntigens, Tumor-Associated, CarbohydrateCell LineGlycosylationHumansMembrane GlycoproteinsMiceNeoplasmsPodoplaninReceptors, Chimeric AntigenAntigens, NeoplasmAntigens, Tumor-Associated, CarbohydrateMembrane GlycoproteinsPDPN protein, humanPodoplaninReceptors, Chimeric AntigenTn antigenCancer gene therapyGlycobiologyImmunologyT cells

Identifiers

PMID31672936
PMCPMC6948763
OpenAlexW2982738870

What OpenQuestion holds

Textmetadata
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.