Evidence map›Paper›PMID 42310302›Full record

ArticleNature communications2026

IDH1-R132H enhances oncolytic HSV-1 therapy by facilitating viral entry and immune activation in glioma.

Eleni Panagioti, Hunter J Kelley, Alexander L Ling, Leinal Sejour, Shikha Saini, William F Goins, Daniel Roberts, Sotiris Sotiriou, J Bryan Iorgulescu, Karen O Dixon and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. 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
–field-weighted citation impact
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.

  1. Precision virotherapy for IDH-mutant astrocytoma.Molecular therapy. Oncology · 2026
    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

18 authors.

Eleni PanagiotiHarvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. epanagio@bidmc.harvard.edu.ORCID 0000-0002-7574-1378
Hunter J KelleyHarvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4124-9948
Alexander L LingHarvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Leinal SejourDepartment of Pathology, HMS Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Cancer Research Institute, Boston, MA, USA.
Shikha SainiHarvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
William F GoinsDepartment of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Daniel RobertsDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Sotiris SotiriouDepartment of Pathology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
J Bryan IorgulescuMolecular Diagnostics Laboratory, Division of Pathology and Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Karen O DixonGene Lay Institute for Immunology and Inflammation at Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7811-5439
Michael B YaffeDepartment of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ioannis S VlachosDepartment of Pathology, HMS Initiative for RNA Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Cancer Research Institute, Boston, MA, USA.ORCID 0000-0002-8849-808X
Maria G CastroDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Sean E LawlerDepartment of Pathology and Laboratory Medicine, Legorreta Cancer Center, Brown University, Providence, RI, USA.
Gordon J FreemanDepartment of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-7210-5616
Vijay K KuchrooGene Lay Institute for Immunology and Inflammation at Brigham and Women's Hospital, Mass General Hospital and Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-7177-2110
E Antonio Chiocca *Harvey Cushing Neuro-oncology Laboratories, Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. eachiocca@mgb.org.ORCID 0000-0001-5183-1670
Charles H Cook *Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. chcook@bidmc.harvard.edu.ORCID 0000-0003-4446-3616

Funding

The Tumor Microenvironmental Barrier to Effective Viral OncolysisP01CA163205 · NCI · OHIO STATE UNIVERSITY · PI Xiaokui Mo · 2013 to 2026
$26.0M
Understanding and Overcoming T cell Immunosuppression in GlioblastomaP01CA236749 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI E. Antonio Chiocca · 2020 to 2026
$19.5M
Preclinical Toxicity Evaluation of a Potent Oncolytic VirusU01NS061811 · NINDS · OHIO STATE UNIVERSITY · PI CHIOCCA, E. ANTONIO · 2008 to 2012
$4.6M
Defining the role of cytomegalovirus in glioblastoma therapiesR01CA263324 · NCI · BROWN UNIVERSITY · PI CHARLES H COOK, Sean Edward Lawler · 2022 to 2026
$3.4M
Oncolytic Virus Therapeutic Responses Occur from Changes in the Glioblastoma Immune MicroenvironmentR01NS110942 · NINDS · BRIGHAM AND WOMEN'S HOSPITAL · PI E. Antonio Chiocca, Hiroshi Nakashima · 2019 to 2026
$3.4M
Beth Israel Deaconess Medical Center (BIDMC) GRT65864NCI NIH HHS P01 CA163205NCI NIH HHS P01 CA236749NCI NIH HHS R01 CA263324NINDS NIH HHS R01 NS110942NINDS NIH HHS U01 NS061811
6 · The paper itself

Abstract

Oncolytic virotherapy represents a promising yet under-explored approach for precision cancer treatment, particularly when tailored to tumor-specific molecular profiles. Patients with high-grade isocitrate dehydrogenase (IDH) mutant astrocytomas have limited treatment options and poor prognoses. Here, we investigate the therapeutic efficacy of rQNestin34.5 v.2 (CAN-3110), an engineered oncolytic herpes simplex virus 1 (oHSV-1), in IDH1-R132H-mutant diffuse gliomas. We demonstrate that the IDH1-R132H mutation enhances glioma susceptibility to viral infection through upregulation of Nectin-1, the main HSV-1 entry receptor. Concurrently, IDH1-R132H-driven DNA hypermethylation suppresses interferon (IFN) signaling, creating a permissive microenvironment that facilitates viral replication and tumor cell apoptosis. In immunocompetent murine glioma models, intratumoral administration of rQNestin34.5 v.2 induces robust antitumor immune activation, including increased immune infiltration and systemic IFN-γ release. However, elevated expression of poliovirus receptor (PVR) and the immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on tumor-infiltrating leukocytes suggests a potential resistance mechanism to virotherapy. Combining rQNestin34.5 v.2 with TIGIT blockade enhances therapeutic efficacy compared to monotherapy, identifying IDH1-R132H as a potential predictive biomarker for oncolytic virotherapy response.

Indexed as

Brain NeoplasmsGliomaHerpesvirus 1, HumanIsocitrate DehydrogenaseOncolytic VirotherapyVirus InternalizationAnimalsCell Line, TumorDNA MethylationFemaleHumansMiceMutationNectinsOncolytic VirusesVirus ReplicationIsocitrate DehydrogenaseNECTIN1 protein, humanNectin1 protein, mouseNectins

Identifiers

PMID42310302
PMCPMC13434784

What OpenQuestion holds

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Registered trials

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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.