Evidence map›Paper›PMID 26962017›Full record

ArticleNeuro-oncology2016

M011L-deficient oncolytic myxoma virus induces apoptosis in brain tumor-initiating cells and enhances survival in a novel immunocompetent mouse model of glioblastoma.

Alexandra Pisklakova, Brienne McKenzie, Franz Zemp, Xueqing Lun, Rajappa S Kenchappa, Arnold B Etame, Masmudur M Rahman, Karlyne Reilly, Shari Pilon-Thomas, Grant McFadden and 2 more

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Article in Neuro-oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

34 citing papers in PubMed, 54 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

12 authors at 5 institutions in 2 countries.

Alexandra PisklakovaDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Brienne McKenzieDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Franz ZempDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Xueqing LunDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Rajappa S KenchappaDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Arnold B EtameDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Masmudur M RahmanDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Karlyne ReillyDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Shari Pilon-ThomasDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Grant McFaddenDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Ebba KurzDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
Peter A ForsythDepartment of Neuro-Oncology and Tumor Biology, Moffitt Cancer Center, Tampa, Florida (A.P., R.S.K., A.B.E., P.A.F.); Southern Alberta Cancer Research Institute, University of Calgary, Calgary, Alberta, Canada (B.M., F.Z., X.L., E.K., P.A.F.); Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida (M.M.R., G.M.); Center for Cancer Research, National Cancer Institute, Bethesda, Maryland (K.R.); Department of Immunology, Moffitt Cancer Center, Tampa, Florida (S.P.-T.).
University of Florida · USCenter for Cancer Research · USMoffitt Cancer Center · USNational Cancer Institute · USUniversity of Calgary · CA

Funding

TRANSLATIONAL RESEARCHP30CA076292 · NCI · UNIVERSITY OF SOUTH FLORIDA · PI KENNETH Lynn WRIGHT · 1998 to 2026
$93.5M
NCI NIH HHS P30 CA076292
6 · The paper itself

Abstract

backgroundMyxoma virus (MYXV) is a promising oncolytic agent and is highly effective against immortalized glioma cells but less effective against brain tumor initiating cells (BTICs), which are believed to mediate glioma development/recurrence. MYXV encodes various proteins to attenuate host cell apoptosis, including an antiapoptotic Bcl-2 homologue known as M011L. Such proteins may limit the ability of MYXV to kill BTICs, which have heightened resistance to apoptosis. We hypothesized that infecting BTICs with an M011L-deficient MYXV construct would overcome BTIC resistance to MYXV.

methodsWe used patient-derived BTICs to evaluate the efficacy of M011L knockout virus (vMyx-M011L-KO) versus wild-type MYXV (vMyx-WT) and characterized the mechanism of virus-induced cell death in vitro. To extend our findings in a novel immunocompetent animal model, we derived, cultured, and characterized a C57Bl/6J murine BTIC (mBTIC0309) from a spontaneous murine glioma and evaluated vMyx-M011L-KO efficacy with and without temozolomide (TMZ) in mBTIC0309-bearing mice.

resultsWe demonstrated that vMyx-M011L-KO induces apoptosis in BTICs, dramatically increasing sensitivity to the virus. vMyx-WT failed to induce apoptosis as M011L protein prevented Bax activation and cytochrome c release. In vivo, intracranial implantation of mBTIC0309 generated tumors that closely recapitulated the pathological and molecular profile of human gliomas. Treatment of tumor-bearing mice with vMyx-M011L-KO significantly prolonged survival in immunocompetent-but not immunodeficient-mouse models, an effect that is significantly enhanced in combination with TMZ.

conclusionsOur data suggest that vMyx-M011L-KO is an effective, well-tolerated, proapoptotic oncolytic virus and a strong candidate for clinical translation.

Indexed as

apoptosisbrain tumor-initiating cellsgliomaoncolytic virus

Identifiers

PMID26962017
PMCPMC4933479
OpenAlexW2295866100

What OpenQuestion holds

Textmetadata
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.