Evidence map›Paper›PMID 38267626›Full record

ArticleCancer gene therapy2024

The safety and efficacy of systemic delivery of a new liver-de-targeted TGFβ signaling inhibiting adenovirus in an immunocompetent triple negative mouse mammary tumor model.

Soon Cheon Shin, Renee E Vickman, Beniamin Filimon, Yuefeng Yang, Zebin Hu, Kathy A Mangold, Bellur S Prabhakar, Hans Schreiber, Weidong Xu

Open access · hybridAbstract read
In one paragraph

Article in Cancer gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.1field-weighted citation impact, top 22% 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

1 citing paper in PubMed, 2 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Soon Cheon Shin *Cancer Gene Therapy Program, Department of Medicine, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA.
Renee E Vickman *Center for Personalized Cancer Care, Department of Surgery, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA.ORCID 0000-0002-5614-9221
Beniamin FilimonCancer Gene Therapy Program, Department of Medicine, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA.
Yuefeng YangCancer Gene Therapy Program, Department of Medicine, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA.ORCID 0009-0007-6518-660X
Zebin HuCancer Gene Therapy Program, Department of Medicine, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA.
Kathy A MangoldDepartment of Pathology and Laboratory Medicine, NorthShore University HealthSystem, Endeavor Health Medical Group, Evanston, IL, USA.
Bellur S PrabhakarDepartment of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL, USA.ORCID 0000-0001-9815-9850
Hans SchreiberDepartment of Pathology, The University of Chicago, Chicago, IL, USA.
Weidong XuCancer Gene Therapy Program, Department of Medicine, NorthShore University HealthSystem, an Academic Affiliate of the University of Chicago Pritzker School of Medicine, Endeavor Health Medical Group, Evanston, IL, USA. WXu@northshore.org.ORCID 0000-0002-7571-7917
NorthShore University HealthSystem · USUniversity of Chicago · USUniversity of Illinois Urbana-Champaign · US

Funding

Systemic delivery of an oncolytic adenovirus targeting TGFβ to enhance anti-PD-1 and anti-CTLA-4 therapy for triple negative breast cancerR01CA248574 · NCI · ENDEAVOR HEALTH CLINICAL OPERATIONS · PI XU, WEIDONG · 2021 to 2025
$2.0M
Oncolytic Adenovirus-sTGFbetaRIIFc Targeting Breast Cancer Bone MetastasisR01CA127380 · NCI · NORTHSHORE UNIVERSITY HEALTHSYSTEM · PI SETH, PREM · 2007 to 2011
$1.4M
NCI NIH HHS R01 CA127380NCI NIH HHS R01 CA248574
6 · The paper itself

Abstract

Aberrant TGFβ signaling is linked to metastasis and tumor immune escape of many cancers including metastatic triple negative breast cancer (mTNBC). Previously, we have found that oncolytic adenoviruses expressing a TGFβ signaling inhibitory protein (sTGFβRIIFc) induced immune activation in a mouse TNBC (4T1) immunocompetent subcutaneous model with intratumoral injection. Systemic administration of adenoviruses can be a superior route to treat mTNBC but faces the challenges of increased toxicity and viral clearance. Thus, we created a liver-de-targeted sTGFβRIIFc- and LyP-1 peptide-expressing adenovirus (mHAdLyp.sT) with enhanced breast cancer cell tropism. Its safety and immune response features were profiled in the 4T1 model. Our data showed that the systemic administration of mHAdLyp.sT resulted in reduced hepatic and systemic toxicity. mHAdLyp.sT was also effective in increasing Th1 cytokines and anti-tumor cell populations by cytokine analysis, spleen/tumor qRT-PCR, and flow cytometry. We further tested the therapeutic effects of mHAdLyp.sT alone and in combination with immune checkpoint inhibitors (ICIs). mHAdLyp.sT alone and with all ICI combinations elicited significant inhibition of lung metastasis by histological analysis. When mHAdLyp.sT was combined with both anti-PD-1 and anti-CTLA-4 antibodies, primary 4T1 tumor growth was also significantly inhibited. We are confident in advancing this new treatment option for mTNBC.

Indexed as

Adenoviridae InfectionsMammary Neoplasms, AnimalTriple Negative Breast NeoplasmsAdenoviridaeAnimalsCell Line, TumorCytokinesHumansLiverMiceSignal TransductionTransforming Growth Factor betaCytokinesTransforming Growth Factor beta

Identifiers

PMID38267626
PMCPMC11016465
OpenAlexW4391173433

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.