Evidence map›Paper›PMID 41061048›Full record

ArticleScience translational medicine2025

Serial multiomics uncovers anti-glioblastoma responses not evident by routine clinical analyses.

Alexander L Ling, Jennifer Gantchev, Michael C Prabhu, Sreyashi Basu, Ryuhjin Ahn, Alicia D'Souza, Nafisa Masud, Anna Ball, Odysseas Nikas, Genaro R Villa and 34 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Article
  2. Accelerating discovery: Transformative clinical trial models in neuro-oncology.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
  3. Article
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  5. Article
  6. Article
  7. Review
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  10. Review
  11. Now you see me; now you don't.Science translational medicine · 2025
    Review
  12. Review
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

44 authors.

Alexander L LingHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-6194-9875
Jennifer GantchevSurgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5236-0671
Michael C PrabhuDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Sreyashi BasuJames P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0002-5028-3833
Ryuhjin AhnKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-9788-4401
Alicia D'SouzaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-7635-7573
Nafisa MasudHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Anna BallHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0009-0000-7725-4330
Odysseas NikasHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Genaro R VillaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-9461-2291
Michael S ReganSurgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5252-2829
Gerard BaquerSurgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-4433-4972
Georges AyoubDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-1694-6779
Charles A WhittakerKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-2400-0094
Zaki Abou-MradDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0001-6387-8396
Andres SantosHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-7250-0184
Charles P CouturierSurgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.
Dina ElharouniDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-1488-0347
Jayne VogelzangDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-8249-3600
Kenny K H YuDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-2394-4990
Hong ChenJames P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0003-2315-0645
Zhong HeJames P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0002-7369-9989
Wen JiangDepartment of Radiation Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0001-9154-633X
Calixto Hope LucasDepartment of Pathology, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.ORCID 0000-0002-8347-9592
Haley E SaxDepartment of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0009-0000-9277-086X
Frederick F LangDepartment of Neurosurgery, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0003-3747-873X
Vinay K PuduvalliDepartment of Neuro-Oncology, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0001-8396-9500
Viviane TabarDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0002-1284-1670
Cameron W BrennanDepartment of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.ORCID 0000-0003-4064-8891
Adrienne BoireDepartment of Neurology, Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Matthias HoldhoffDivision of Neuro-Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.ORCID 0000-0002-3285-3484
Chetan BettegowdaDepartment of Neurosurgery, Johns Hopkins University Medical Center, Baltimore, MD 21205, USA.ORCID 0000-0001-9991-7123
Michael CimaKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Isaac H SolomonDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-3432-0902
Ying YuanDepartment of Biostatistics, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.
Paul P TakCandel Therapeutics Inc., Needham, MA 02494, USA.ORCID 0000-0002-3532-5409
Accelerating GBM Therapies TeamLabAccelerating GBM Therapies TeamLab, Cambridge, MA 02142, USA.
Padmanee SharmaJames P. Allison Institute, University of Texas MD Anderson Cancer Hospital, Houston, TX 77030, USA.ORCID 0000-0003-4658-055X
Forest M WhiteKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0002-1545-1651
Keith L LigonDepartment of Pathology, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0002-7733-600X
Nathalie Y R AgarSurgical Brain Mapping and Molecular Imaging Laboratory, Department of Neurosurgery, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0003-3149-3146
David A ReardonCenter for Neuro-Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-6674-0157
Giacomo OliveiraBroad Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.ORCID 0000-0001-7435-5603
E Antonio ChioccaHarvey Cushing Neuro-Oncology Laboratories, Department of Neurosurgery and Center for Tumors of the Nervous System, Mass General Brigham Cancer Institute and Harvard Medical School, Boston, MA 02115, USA.ORCID 0000-0001-5183-1670

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
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
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
NCI NIH HHS P01 CA163205NCI NIH HHS P01 CA236749NCI NIH HHS P30 CA008748NINDS NIH HHS R01 NS110942
6 · The paper itself

Abstract

Recurrent glioblastoma (rGBM) remains incurable. One barrier to the development of effective rGBM therapies is the difficulty in collecting posttreatment tumor tissue. Serial multiomic assays from longitudinal rGBM biopsies may uncover tumor responses to a treatment. Here, we obtained 97 serial rGBM biopsy cores over 4 months from the first two patients participating in a clinical trial of repeated intratumoral dosing of the immunotherapeutic agent CAN-3110. Multiomic analysis of the biopsy cores revealed therapeutic effects, including longitudinal and spatial reshaping of the rGBM's microenvironment, expansion of new T cell tissue-resident effector memory clonotypes against CAN-3110 epitopes and other undetermined antigens, and expression of human leukocyte antigen (HLA)-presented immunopeptides, including cancer testis antigens. Moreover, serial integrated multimodal analyses provided evidence of therapeutic responses to CAN-3110 despite traditional magnetic resonance imaging indicating progression. Clinically, the two treated patients achieved a pathologic response or stable clinical disease, respectively. These results show the value of longitudinal tissue sampling to understand rGBM's evolution during administration of an investigational therapy.

Indexed as

Brain NeoplasmsGlioblastomaBiopsyFemaleHumansMagnetic Resonance ImagingMaleMiddle AgedMultiomicsTreatment OutcomeTumor Microenvironment

Identifiers

PMID41061048
PMCPMC13574239

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.