Evidence map›Paper›PMID 32145202›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020

Transient Inhibition of PI3Kδ Enhances the Therapeutic Effect of Intravenous Delivery of Oncolytic Vaccinia Virus.

Mark S Ferguson, Louisa S Chard Dunmall, Rathi Gangeswaran, Giulia Marelli, James R Tysome, Emily Burns, Maria A Whitehead, Ezra Aksoy, Ghassan Alusi, Crispin Hiley and 4 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.9field-weighted citation impact, top 5% 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

37 citing papers in PubMed, 42 citations in OpenAlex.

  1. Review
  2. Oncolytic virus M1 reinvigorates CD8Cellular & molecular immunology · 2026
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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

14 authors at 4 institutions in 2 countries.

Mark S FergusonCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Louisa S Chard DunmallCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Rathi GangeswaranCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Giulia MarelliCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
James R TysomeCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK; Otolaryngology Department, Cambridge University Hospitals, Cambridge, UK.
Emily BurnsCentre for Cell Signalling, Barts Cancer Institute, Queen Mary University of London, London, UK.
Maria A WhiteheadUCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK.
Ezra AksoyWilliam Harvey Research Institute, Queen Mary University of London, London, UK.
Ghassan AlusiDepartment of Otolaryngology, Head & Neck Surgery, Barts Health NHS Trust, The Royal London Hospital, Whitechapel Road, Whitechapel, London E1 1BB, UK.
Crispin HileyCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Jay AhmedCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK.
Bart VanhaesebroeckUCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6BT, UK.
Nicholas R LemoineCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
Yaohe WangCentre for Molecular Oncology, Barts Cancer Institute, Queen Mary University of London, London, UK; National Centre for International Research in Cell and Gene Therapy, Sino-British Research Centre for Molecular Oncology, Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China. Electronic address: yaohe.wang@qmul.ac.uk.
Queen Mary University of London · GBCRUK Lung Cancer Centre of Excellence · GBRoyal London Hospital · GBZhengzhou University · CN

Funding

Cancer Research UK 15965Cancer Research UK 25722Cancer Research UK A12008Cancer Research UK A25137Cancer Research UK C16420/A16373Cancer Research UK C23338/A2572Department of HealthMedical Research Council MR/M015696/1Medical Research Council MR/M023230/1Medical Research Council MR/N027655/1Versus Arthritis 19867
6 · The paper itself

Abstract

Tumor-targeting oncolytic viruses such as vaccinia virus (VV) are attractive cancer therapeutic agents that act through multiple mechanisms to provoke both tumor lysis and anti-tumor immune responses. However, delivery of these agents remains restricted to intra-tumoral administration, which prevents effective targeting of inaccessible and disseminated tumor cells. In the present study we have identified transient pharmacological inhibition of the leukocyte-enriched phosphoinositide 3-kinase δ (PI3Kδ) as a novel mechanism to potentiate intravenous delivery of oncolytic VV to tumors. Pre-treatment of immunocompetent mice with the PI3Kδ-selective inhibitor IC87114 or the clinically approved idelalisib (CAL-101), prior to intravenous delivery of a tumor-tropic VV, dramatically improved viral delivery to tumors. This occurred via an inhibition of viral attachment to, but not internalization by, systemic macrophages through perturbation of signaling pathways involving RhoA/ROCK, AKT, and Rac. Pre-treatment using PI3Kδ-selective inhibitors prior to intravenous delivery of VV resulted in enhanced anti-tumor efficacy and significantly prolonged survival compared to delivery without PI3Kδ inhibition. These results indicate that effective intravenous delivery of oncolytic VV may be clinically achievable and could be useful in improving anti-tumor efficacy of oncolytic virotherapy.

Indexed as

AdenineAdministration, IntravenousAnimalsAntineoplastic AgentsCell Line, TumorCell SurvivalClass I Phosphatidylinositol 3-KinasesCombined Modality TherapyFemaleImmunotherapyMiceMice, Inbred BALB COncolytic VirotherapyOncolytic VirusesPurinesQuinazolinesAdenineAntineoplastic AgentsClass I Phosphatidylinositol 3-KinasesIC 87114idelalisibPurinesQuinazolinesQuinazolinonesbreast cancercolorectal cancerimmunotherapyintravenous deliverymacrophageoncolytic virusphosphoinositide 3-kinase δvaccinia virus

Identifiers

PMID32145202
PMCPMC7210704
OpenAlexW3006950074

What Socratic holds

Textmetadata
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 Socratic graph.