Summary: Researchers have developed a personalized DNA cancer vaccine that produced encouraging results in an early-stage clinical trial for glioblastoma, showing safety, broad immune activation, and signals of improved survival in patients with aggressive, unmethylated tumors.
The vaccine, GNOS-PV01, was well tolerated and provoked robust immune responses. In a small phase 1 trial, the treatment appeared to extend recurrence-free and overall survival compared with historical outcomes for this hard-to-treat brain cancer.
Key Research Findings
- DNA platform advantage: The GNOS-PV01 DNA vaccine can encode up to 40 distinct neoantigens per patient—about twice the number targeted by previous cancer vaccines—allowing a broader immune attack on tumor-specific proteins.
- Converting cold tumors to hot: Glioblastoma typically creates an immunosuppressive, or “cold,” tumor microenvironment. This vaccine platform both targets tumor proteins and helps transform that environment into a more immune-reactive, or “hot,” state.
- Broad, multi-region targeting: Neoantigens were chosen from different regions of each tumor to reduce the likelihood that the cancer could escape immune detection by losing individual targets.
- Clinical outcomes:
- Six months: Two-thirds of participants had no disease progression at six months after surgery.
- One year: Approximately 66.7% of participants were alive at 12 months, versus a historical average near 40%.
- Two years: About one-third of participants were alive at 24 months—roughly double the expected rate historically.
- Long-term survivor: One patient remains recurrence-free nearly five years after diagnosis.
- Safety: No serious adverse events, unexpected toxicities, or dose-limiting toxicities were observed when GNOS-PV01 was given after surgery and alongside standard radiation therapy.
Source: WUSTL
A personalized DNA vaccine to treat glioblastoma—a fast-growing, typically fatal brain cancer—demonstrated safety and strong immune activation in a phase 1 trial led in part by Washington University School of Medicine in St. Louis. The trial focused on patients with the unmethylated MGMT subtype, a form that responds poorly to standard chemotherapy and is associated with particularly poor outcomes.
Investigators engineered synthetic DNA constructs encoding a selection of tumor-specific neoantigens unique to each patient. Those constructs were administered as a therapeutic vaccine following surgical resection and during the patient’s postoperative radiation period. The study reports that nearly all participants who were not concurrently on immune-suppressing steroids showed activation and expansion of tumor-specific peripheral T cells.
Lead author Tanner M. Johanns, MD, PhD, emphasized the rationale for using a DNA-based platform: its capacity to encode many neoantigens could generate broader immune responses than other vaccine approaches that target fewer proteins. By presenting up to 40 neoantigens drawn from multiple tumor regions, the vaccine aims to reduce the cancer’s ability to evade immune detection as it evolves.
More targets, more chances for success
The GNOS-PV01 vaccine relies on personalized selection of neoantigens—proteins produced only by an individual’s tumor that the immune system can learn to recognize. A computational algorithm developed at Washington University helped identify and prioritize neoantigens from tumor sequencing data. Vaccine manufacturing was performed during the patient’s recovery and radiation treatment, with injections beginning on average about 10 weeks after surgery and then given on a scheduled regimen during follow-up.
The phase 1 GT-20 trial enrolled nine adults with newly diagnosed glioblastoma treated at a single center. Each patient received a personalized DNA vaccine encoding between 17 and 40 neoantigens. The protocol achieved its primary aims of demonstrating feasibility and safety and met secondary endpoints related to immunogenicity and preliminary clinical activity.
Measured outcomes included median progression-free survival of 8.5 months and median overall survival of 16.3 months. The vaccine induced measurable tumor-specific T-cell responses in nearly all evaluated patients, with the notable exception of a participant receiving the steroid dexamethasone, which suppresses immune activity.
An investment in the future
The report includes patient perspectives, such as Kim Garland, a retired school nurse whose tumor was removed in 2021 and who volunteered for the trial. Kim’s tumor was the unmethylated MGMT subtype; she remains recurrence-free nearly five years after diagnosis. Her experience underscores the potential clinical and personal impact of novel immunotherapies when they produce durable responses.
Co-senior authors and collaborators noted that neoantigen-targeted personalized vaccines represent a promising avenue for glioblastoma and other cancers, but that larger trials are needed. The research team plans to test GNOS-PV01 in a broader group of patients and to evaluate combination strategies designed to enhance vaccine effectiveness further.
Funding and disclosures: The study received support from multiple sources including the Mark Foundation for Cancer Research Momentum Fellowship, NIH grants from NINDS and other institutes, foundation funds, and in-kind support from Geneos Therapeutics for vaccine development and immune monitoring. Some authors are current or former employees of Geneos Therapeutics. The content reflects the authors’ findings and interpretations.
Key Questions Answered:
Q: How is a “personalized” vaccine actually made?
A: Researchers sequence each patient’s tumor to identify neoantigens—unique cancer proteins. Using computational tools, they select up to 40 targets and manufacture a synthetic DNA construct that instructs the patient’s immune system to recognize and attack cells expressing those neoantigens.
Q: Why is glioblastoma so hard to treat?
A: Glioblastoma creates an immunosuppressive microenvironment and evolves rapidly. Treatments that target only a few proteins allow the tumor to escape by downregulating those targets. A multivalent vaccine that targets many neoantigens makes immune escape more difficult.
Q: Does this work for all types of brain cancer?
A: This trial focused on unmethylated MGMT glioblastoma, the subtype least responsive to standard chemotherapy. Future studies aim to evaluate the vaccine across a wider range of glioblastoma subtypes and in larger patient populations.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The original journal paper was reviewed in full.
- Additional context was provided by the editorial staff.
About this brain cancer research news
Author: Mark Reynolds
Source: WUSTL
Contact: Mark Reynolds – WUSTL
Image: Image credit: Neuroscience News
Original Research: Open access. “Adjuvant personalized multivalent neoantigen DNA vaccination induces tumor-specific immune responses in newly diagnosed glioblastoma patients” by Garfinkle EAR et al., published in Nature Cancer. DOI: 10.1038/s43018-026-01163-w
Abstract
Adjuvant personalized multivalent neoantigen DNA vaccination induces tumor-specific immune responses in newly diagnosed glioblastoma patients
Glioblastoma carries a median survival of approximately 12–18 months. Neoantigen-based vaccines have shown initial promise but have generally produced limited immunogenicity. This open-label, single-arm phase 1 trial (GT-20) evaluated GNOS-PV01—a personalized, DNA-based neoantigen vaccine—administered after surgery and radiation in patients with unmethylated MGMT glioblastoma. Nine patients received vaccines encoding 17–40 neoantigens per individual. No serious or dose-limiting toxicities were observed. The vaccine induced expansion of peripheral T cells in all evaluable patients except one on dexamethasone. Six-month progression-free survival and 12-month overall survival were each observed in 66.7% of participants. Median progression-free survival was 8.5 months; median overall survival was 16.3 months; 24-month survival was 33%, and one patient remained alive more than four years after initial surgery. The study met prespecified endpoints and supports further evaluation of GNOS-PV01 as a component of glioblastoma immunotherapy. ClinicalTrials.gov identifier: NCT04015700.