Evidence map›Paper›PMID 29327109›Full record

ArticleCancer immunology, immunotherapy : CII2018

A novel biologic platform elicits profound T cell costimulatory activity and antitumor immunity in mice.

Joseph M Ryan, Payal Mittal, Antoine Menoret, Julia Svedova, Jeffrey S Wasser, Adam J Adler, Anthony T Vella

Abstract read
In one paragraph

Article in Cancer immunology, immunotherapy : CII, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Optimal CD8Nature communications · 2022
    Article
  3. Article
  4. Engineering Platforms for T Cell Modulation.International review of cell and molecular biology · 2018
    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

7 authors.

Joseph M RyanDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA.
Payal MittalDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA.
Antoine MenoretDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA.
Julia SvedovaDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA.
Jeffrey S WasserDepartment of Medicine, School of Medicine, UConn Health, Farmington, CT, 06030, USA.
Adam J AdlerDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA. aadler@uchc.edu.ORCID http://orcid.org/0000-0002-7970-155X
Anthony T VellaDepartment of Immunology, School of Medicine, UConn Health, Farmington, CT, 06030, USA. vella@uchc.edu.

Funding

Redirecting T Cell Responses to Self/Tumor Antigens Using Enforced CostimulationR01CA109339 · NCI · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ADLER, ADAM J, VELLA, ANTHONY T · 2004 to 2015
$2.9M
Breaking Tolerance to Induce Tumor-Specific Cytotoxic CD4 Th1 CellsR01AI094640 · NIAID · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI ADLER, ADAM J, VELLA, ANTHONY T · 2012 to 2016
$1.9M
National Institute of Allergy and Infectious Diseases 094640NCI NIH HHS 109339NCI NIH HHS R01 CA109339NIAID NIH HHS R01 AI094640
6 · The paper itself

Abstract

Combination immunotherapies utilizing complementary modalities that target distinct tumor attributes or immunosuppressive mechanisms, or engage different arms of the antitumor immune response, can elicit greater therapeutic efficacy than the component monotherapies. Increasing the number of agents included in a therapeutic cocktail can further increase efficacy, however, this approach poses numerous challenges for clinical translation. Here, a novel platform to simplify combination immunotherapy by covalently linking immunotherapeutic agonists to the costimulatory receptors CD134 and CD137 into a single heterodimeric drug, "OrthomAb", is shown. This reagent not only retains costimulatory T cell activity, but also elicits unique T cell functions that are not programmed by either individual agonist, and preferentially expands effector T cells over Tregs. Finally, in an aggressive melanoma model OrthomAb elicits better therapeutic efficacy compared to the unlinked agonists. This demonstration that two drugs can be combined into one provides a framework for distilling complex combination drug cocktails into simpler delivery platforms.

Indexed as

ImmunotherapyAnimalsAntibodies, MonoclonalCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationFemaleLymphocyte ActivationMelanoma, ExperimentalMiceMice, Inbred C57BLReceptors, OX40Tumor Cells, CulturedTumor Necrosis Factor Receptor Superfamily, Member 9Antibodies, MonoclonalReceptors, OX40Tnfrsf4 protein, mouseTumor Necrosis Factor Receptor Superfamily, Member 94-1BBCancer immunotherapyCD134CD137CostimulationOX40

Identifiers

PMID29327109
PMCPMC5862768

What OpenQuestion holds

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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.