Evidence map›Paper›PMID 36710369›Full record

ArticleCPT: pharmacometrics & systems pharmacology2023

Quantitative systems pharmacology model of GITR-mediated T cell dynamics in tumor microenvironment.

Yan Ji, Kumpal Madrasi, Deborah A Knee, Lore Gruenbaum, Joshua F Apgar, John M Burke, Bruce Gomes

Open access · goldAbstract read
In one paragraph

Article in CPT: pharmacometrics & systems pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.5field-weighted citation impact, top 18% 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, 9 citations in OpenAlex.

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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 at 5 institutions in 2 countries.

Yan JiNovartis Pharmaceuticals Corporation, East Hanover, New Jersey, USA.ORCID 0000-0001-9569-0574
Kumpal MadrasiSanofi, Bridgewater, New Jersey, USA.
Deborah A KneeNovartis Institutes for Biomedical Research, San Diego, California, USA.
Lore GruenbaumTherapy Acceleration Program, The Leukemia & Lymphoma Society, Rye Brook, New York, USA.ORCID 0000-0002-7928-5496
Joshua F ApgarApplied Biomath LLC, Concord, Massachusetts, USA.ORCID 0000-0002-3396-1874
John M BurkeApplied Biomath LLC, Concord, Massachusetts, USA.
Bruce GomesNovartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA.
Applied BioMath (United States) · USNovartis (United States) · USGenomics Institute of the Novartis Research Foundation · USLeukemia and Lymphoma Society · USSanofi (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

T cell interaction in the tumor microenvironment is a key component of immuno-oncology therapy. Glucocorticoid-induced tumor necrosis factor receptor (TNFR)-related protein (GITR) is expressed on immune cells including regulatory T cells (Tregs) and effector T cells (Teffs). Preclinical data suggest that agonism of GITR in combination with Fc-γ receptor-mediated depletion of Tregs results in increased intratumoral Teff:Treg ratio and tumor shrinkage. A novel quantitative systems pharmacology (QSP) model was developed for the murine anti-GITR agonist antibody, DTA-1.mIgG2a, to describe the kinetics of intratumoral Tregs and Teffs in Colon26 and A20 syngeneic mouse tumor models. It adequately captured the time profiles of intratumoral Treg and Teff and serum DTA-1.mIgG2a and soluble GITR concentrations in both mouse models, and described the response differences between the two models. The QSP model provides a quantitative understanding of the trade-off between maximizing Treg depletion versus Teff agonism, and offers insights to optimize drug design and dose regimen.

Indexed as

NeoplasmsTumor MicroenvironmentAnimalsDisease Models, AnimalGlucocorticoid-Induced TNFR-Related ProteinMiceNetwork PharmacologyReceptors, Tumor Necrosis FactorT-Lymphocytes, RegulatoryGlucocorticoid-Induced TNFR-Related ProteinReceptors, Tumor Necrosis Factor

Identifiers

PMID36710369
PMCPMC10014051
OpenAlexW4318455103

What OpenQuestion holds

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LicenceCC BY-NC-ND
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.