Evidence map›Paper›PMID 34572822›Full record

ArticleCancers2021

CD18 Antibody Application Blocks Unwanted Off-Target T Cell Activation Caused by Bispecific Antibodies.

Joseph Kauer, Fabian Vogt, Ilona Hagelstein, Sebastian Hörner, Melanie Märklin, Stefanie Maurer, Helmut R Salih, Gundram Jung, Latifa Zekri

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.1field-weighted citation impact, top 50% 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

3 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Article
  3. Optical image-guided therapy of pancreatic cancer with an ultra-small bispecific protein.European journal of nuclear medicine and molecular imaging · 2023
    Article
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

9 authors at 3 institutions in 2 countries.

Joseph KauerGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.ORCID 0000-0003-1632-0167
Fabian VogtGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
Ilona HagelsteinClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.
Sebastian HörnerGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
Melanie MärklinClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-2920-3894
Stefanie MaurerClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.ORCID 0000-0003-2423-3338
Helmut R SalihClinical Collaboration Unit Translational Immunology, German Cancer Consortium (DKTK), Department of Internal Medicine, University Hospital Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-6719-1847
Gundram JungGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.
Latifa ZekriGerman Cancer Consortium (DKTK) and German Cancer Research Center (DKFZ) Partner Site Tübingen, Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, 72076 Tübingen, Germany.ORCID 0000-0002-9844-7948
German Cancer Research Center · DEDeutschen Konsortium für Translationale Krebsforschung · DEMemorial Sloan Kettering Cancer Center · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4M
Deutsche Forschungsgemeinschaft SA1360/7-3Deutsche Forschungsgemeinschaft SA1360/9-1Deutsche Krebshilfe 111828Deutsche Krebshilfe 70112914Deutschen Konsortium für Translationale Krebsforschung n/aGermany's Excellence Strategy EXC 2180/1NCI NIH HHS P30 CA008748Wilhelm Sander-Stiftung 2007.115.3
6 · The paper itself

Abstract

T cell-recruiting bispecific antibodies (bsAbs) are successfully used for the treatment of cancer. However, effective treatment with bsAbs is so far hampered by severe side effects, i.e., potentially life-threatening cytokine release syndrome. Off-target T cell activation due to binding of bispecific CD3 antibodies to T cells in the absence of target cells may contribute to excessive cytokine release. We report here, in an in vitro setting, that off-target T cell activation is induced by bsAbs with high CD3 binding affinity and increased by endothelial- or lymphoid cells that act as stimulating bystander cells. Blocking antibodies directed against the adhesion molecules CD18/CD54 or CD2/CD58 markedly reduced this type of off-target T cell activation. CD18 blockade-in contrast to CD2-did not affect the therapeutic activity of various bsAbs. Since CD18 antibodies have been shown to be safely applicable in patients, blockade of this integrin holds promise as a potential target for the prevention of unwanted off-target T cell activation and allows the application of truly effective bsAb doses.

Indexed as

bispecific antibodiesCD18cytokine release syndromeimmunotherapyT cell activation

Identifiers

PMID34572822
PMCPMC8467378
OpenAlexW3200448306

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.