Evidence map›Paper›PMID 42156731›Full record

ArticleNature communications2026

Non-lytic viral immunotherapy induces long-term glioblastoma survival and tumor-specific immunity without eliciting an antiviral response.

Alexander F Haddad, Atul Saha, Sara A Collins, Isabella Lovalvo, Sabraj Gill, Megan L Montoya, Poojan Shukla, Jinpyo Hong, Elaina Wang, Pavlina Chuntova 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. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Alexander F HaddadDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Atul SahaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0009-9411-9881
Sara A CollinsDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Isabella LovalvoDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0000-3805-431X
Sabraj GillDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Megan L MontoyaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Poojan ShuklaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Jinpyo HongDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0004-9256-9233
Elaina WangDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Pavlina ChuntovaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Meeki LadDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Robert OsorioDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-7669-2176
Jia-Shu ChenDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Melissa SathavipatDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0009-0002-2114-2094
Saket JainDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Eric ChalifDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.
Noriyuki KasaharaDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9186-911X
Manish K AghiDepartment of Neurological Surgery, University of California, San Francisco, San Francisco, CA, USA. manish.aghi@ucsf.edu.ORCID http://orcid.org/0000-0002-2949-2227

Funding

Translational InformaticsP30CA082103 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jennifer Leigh Clarke · 1999 to 2026
$209.7M
Tumor cell and microenvironment changes causing antiangiogenic therapy resistanceR01NS079697 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2013 to 2021
$3.2M
NINDS Research Education Programs for Residents and Fellows in Neurology, Neurosurgery, Neuropathology, Neuroradiology and Emergency Medicine (R25)UE5NS070680 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Scott Andrew Josephson · 2024 to 2026
$2.6M
Modeling and druggable-genome screening of glioblastoma invasion using regional biopsy-guided biomaterials systemsR01CA227136 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI AGHI, MANISH · 2018 to 2022
$2.2M
Retroviral RLI immunomodulatory gene therapy for glioblastomaR01NS123808 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Manish Aghi · 2022 to 2026
$2.1M
Mechanisms of adhesion and invasion in hyaluronic acid matricesR01CA260443 · NCI · UNIVERSITY OF CALIFORNIA BERKELEY · PI KUMAR, SANJAY · 2021 to 2025
$1.8M
PRISM: Precision Radiotherapy and Imaging of Small MammalsS10OD021818 · OD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FADDEGON, BRUCE · 2017 to 2017
$531k
NCI NIH HHS P30 CA082103NCI NIH HHS R01 CA227136NCI NIH HHS R01 CA260443NIH HHS S10 OD021818NINDS NIH HHS R01 NS079697NINDS NIH HHS R01 NS123808NINDS NIH HHS UE5 NS070680U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA260443U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) 5UE5NS070680-15U.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and Stroke (NINDS) R01NS079697
6 · The paper itself

Abstract

Glioblastoma is a lethal brain tumor that is resistant to conventional therapies. Here we present a non-lytic replicating retrovirus (RRV) that delivers an IL-15-receptor-linked fusion protein (RLI) superagonist directly into glioblastoma cells, creating localized immunotherapy biofactories. In orthotopic mouse models, RRV-RLI dramatically suppresses tumor growth, prolongs survival, and induces lasting remission with immunologic memory. Mechanistically, we observe increased CD8⁺ T cell and natural killer cell infiltration and activation, alongside elevated antigen presentation pathways. Combining RRV-RLI with temozolomide, which is standard-of-care chemotherapy for glioblastoma, enhances antitumor immunity. T cell receptor sequencing reveals a polyclonal repertoire of T cells, enhanced by combining RRV-RLI with temozolomide. Analysis of the T-cell repertoire suggests it to be directed against tumor rather than viral antigens, supporting the specificity and re-applicability of our approach. These findings illustrate that RRV-RLI reprograms glioblastoma into an immunostimulatory hub, offering a viral immunotherapy against glioblastoma and potentially other therapy-resistant solid tumors.

Indexed as

Brain NeoplasmsGlioblastomaImmunotherapyRetroviridaeAnimalsCD8-Positive T-LymphocytesCell Line, TumorFemaleHumansImmunologic MemoryInterleukin-15Killer Cells, NaturalMiceMice, Inbred C57BLRecombinant Fusion ProteinsTemozolomideInterleukin-15Recombinant Fusion ProteinsTemozolomide

Identifiers

PMID42156731
PMCPMC13381920

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

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.