Evidence map›Paper›PMID 37509357›Full record

ArticleCancers2023

Generation of Orthotopic Patient-Derived Xenografts in Humanized Mice for Evaluation of Emerging Targeted Therapies and Immunotherapy Combinations for Melanoma.

Chi Yan, Caroline A Nebhan, Nabil Saleh, Rebecca Shattuck-Brandt, Sheau-Chiann Chen, Gregory D Ayers, Vivian Weiss, Ann Richmond, Anna E Vilgelm

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2023. 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
2.3field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.

  1. Pooled it
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  3. Review
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  10. Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024
    Review
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  12. 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 4 institutions in 1 country.

Chi YanDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-8658-7302
Caroline A NebhanDepartment of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37232, USA.
Nabil SalehDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-3694-0681
Rebecca Shattuck-BrandtDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.
Sheau-Chiann ChenDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Gregory D AyersDepartment of Biostatistics, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Vivian WeissDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Ann RichmondDepartment of Pharmacology, Vanderbilt University, Nashville, TN 37232, USA.ORCID 0000-0002-9580-900X
Anna E VilgelmDepartment of Pathology, Ohio State University, Columbus, OH 43210, USA.ORCID 0000-0002-4446-913X
Vanderbilt University · USVanderbilt University Medical Center · USThe Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute · USVA Tennessee Valley Healthcare System · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Translational Therapeutics Research Program (TT)P30CA016058 · NCI · OHIO STATE UNIVERSITY · PI Jennifer A. Woyach · 1985 to 2026
$132.3M
Targeting the NF-kappaB Pathway in MelanomaR01CA116021 · NCI · VANDERBILT UNIVERSITY · PI RICHMOND, ANN, YAN, CHI · 2005 to 2024
$6.7M
Training Program in Stem Cell and Regenerative Developmental BiologyT32HD007502 · NICHD · VANDERBILT UNIVERSITY · PI WRIGHT, CHRISTOPHER V · 1997 to 2022
$5.4M
MELANOMA GROWTH STIMULATORY ACTIVITYR01CA034590 · NCI · VANDERBILT UNIVERSITY · PI RICHMOND, ANN · 1986 to 2017
$5.2M
VOLT (Vanderbilt Oncology Training Program)T32CA217834 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Debra L. Friedman, Douglas B Johnson · 2018 to 2026
$2.7M
Combining senescence-inducing and senolytic agents to improve melanoma therapyR37CA233770 · NCI · VANDERBILT UNIVERSITY · PI VILGELM, ANNA E · 2019 to 2025
$2.4M
Leica Bond RXS10OD023475 · OD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BOYD, KELLI L. · 2018 to 2018
$213k
BLRD VA I01 BX000196BLRD VA IK6 BX005225NCI NIH HHS CA233770; CA116021; CA116021-S1; CA34590;NCI NIH HHS P30 CA016058NCI NIH HHS P30 CA068485NCI NIH HHS P30 CA68485; P30 CA016058NCI NIH HHS R01 CA034590NCI NIH HHS R01 CA116021NCI NIH HHS R37 CA233770NCI NIH HHS T32 CA217834NICHD NIH HHS T32 HD007502NIH HHS S10 OD023475
6 · The paper itself

Abstract

Current methodologies for developing PDX in humanized mice in preclinical trials with immune-based therapies are limited by GVHD. Here, we compared two approaches for establishing PDX tumors in humanized mice: (1) PDX are first established in immune-deficient mice; or (2) PDX are initially established in humanized mice; then established PDX are transplanted to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Preclinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with PDX tumors established from tumors with limited CD8+ T cell content. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in humanized mice before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response.

Indexed as

humanized miceimmunotherapymelanomapatient-derived xenografttargeted therapy

Identifiers

PMID37509357
PMCPMC10377652
OpenAlexW4385068898

What OpenQuestion holds

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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.