Evidence map›Paper›PMID 33500259›Full record

ArticleJournal for immunotherapy of cancer2021

A systemically deliverable Vaccinia virus with increased capacity for intertumoral and intratumoral spread effectively treats pancreatic cancer.

Giulia Marelli, Louisa S Chard Dunmall, Ming Yuan, Carmela Di Gioia, Jinxin Miao, Zhenguo Cheng, Zhongxian Zhang, Peng Liu, Jahangir Ahmed, Rathi Gangeswaran and 2 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal for immunotherapy of cancer, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.

0numbers the graph read from it
0cells of the map it votes in
33citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

33 citing papers in PubMed, 35 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 3 countries.

Giulia Marelli *Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Louisa S Chard Dunmall *Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Ming YuanCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Carmela Di GioiaCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Jinxin MiaoNational Centre for International Research in Cell and Gene Therapy, Zhengzhou University, Zhengzhou, Henan, China.
Zhenguo ChengNational Centre for International Research in Cell and Gene Therapy, Zhengzhou University, Zhengzhou, Henan, China.
Zhongxian ZhangNational Centre for International Research in Cell and Gene Therapy, Zhengzhou University, Zhengzhou, Henan, China.
Peng LiuCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Jahangir AhmedCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Rathi GangeswaranCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Nicholas LemoineCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK.
Yaohe WangCentre for Cancer Biomarkers and Biotherapeutics, Barts Cancer Institute, Queen Mary University of London, London, UK yaohe.wang@qmul.ac.uk.ORCID 0000-0003-2367-6313
Queen Mary University of London · GBZhengzhou University · CN

Funding

Medical Research Council MR/M015696/1Medical Research Council MR/N027655/1
6 · The paper itself

Abstract

backgroundPancreatic cancer remains one of the most lethal cancers and is refractory to immunotherapeutic interventions. Oncolytic viruses are a promising new treatment option, but current platforms demonstrate limited efficacy, especially for inaccessible and metastatic cancers that require systemically deliverable therapies. We recently described an oncolytic vaccinia virus (VV), VVLΔTKΔN1L, which has potent antitumor activity, and a regime to enhance intravenous delivery of VV by pharmacological inhibition of pharmacological inhibition of PI3 Kinase δ (PI3Kδ) to prevent virus uptake by macrophages. While these platforms improve the clinical prospects of VV, antitumor efficacy must be improved.

methodsVVLΔTKΔN1L was modified to improve viral spread within and between tumors via viral B5R protein modification, which enhanced production of the extracellular enveloped virus form of VV. Antitumor immunity evoked by viral treatment was improved by arming the virus with interleukin-21, creating VVL-21. Efficacy, functional activity and synergy with α-programmed cell death protein 1 (α-PD1) were assessed after systemic delivery to murine and Syrian hamster models of pancreatic cancer.

resultsVVL-21 could reach tumors after systemic delivery and demonstrated antitumor efficacy in subcutaneous, orthotopic and disseminated models of pancreatic cancer. The incorporation of modified B5R improved intratumoural accumulation of VV. VVL-21 treatment increased the numbers of effector CD8+ T cells within the tumor, increased circulating natural killer cells and was able to polarize macrophages to an M1 phenotype in vivo and in vitro. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1.

conclusionsIntravenously administered VVL-21 successfully remodeled the suppressive tumor-microenvironment to promote antitumor immune responses and improve long-term survival in animal models of pancreatic cancer. Importantly, treatment with VVL-21 sensitized tumors to the immune checkpoint inhibitor α-PD1. Combination of PI3Kδ inhibition, VVL-21 and α-PD1 creates an effective platform for treatment of pancreatic cancer.

Indexed as

Administration, IntravenousAnimalsCD8-Positive T-LymphocytesCell Line, TumorClass I Phosphatidylinositol 3-KinasesCombined Modality TherapyHumansImmune Checkpoint InhibitorsInterleukin-12MaleMembrane GlycoproteinsMesocricetusMiceOncolytic VirotherapyOncolytic VirusesPancreatic Neoplasms42kDa protein, Vaccinia virusClass I Phosphatidylinositol 3-KinasesImmune Checkpoint InhibitorsInterleukin-12Membrane GlycoproteinsPIK3CD protein, humanProtein Kinase InhibitorsViral Envelope Proteinsimmunomodulationmacrophagesnatural killer T-cellsoncolytic virusestumor microenvironment

Identifiers

PMID33500259
PMCPMC7839893
OpenAlexW3121622320

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.