Summary: Researchers have developed a personalized DNA cancer vaccine that produced encouraging results in an early-stage clinical trial for glioblastoma.
The trial shows that the vaccine, GNOS-PV01, is safe, provokes broad tumor-specific immune responses, and appears to improve survival outcomes for patients with aggressive, unmethylated forms of this usually incurable brain cancer.
Key Research Findings
- The DNA Platform Advantage: This DNA-based vaccine platform can target up to 40 unique cancer proteins (neoantigens) per patient — roughly double the number targeted by earlier cancer vaccine approaches.
- Turning “Cold” Tumors “Hot”: Glioblastoma commonly creates an immune-suppressive, or “cold,” tumor microenvironment. GNOS-PV01 changes that environment to a more inflamed, “hot” state that makes tumors more visible to and vulnerable to immune attack.
- Wide Target Coverage: The vaccine is designed to expose many neoantigens from multiple regions of a tumor. That breadth reduces the chance that the cancer can escape immune detection by losing a small number of targets.
- Survival Milestones:
- Six months: Two-thirds of participants showed no disease progression at six months.
- One year: Two-thirds of patients were alive at 12 months, versus a historical average near 40%.
- Two years: One-third of participants were alive at 24 months, approximately double the historical rate for this population.
- Long-term: One participant remains recurrence-free nearly five years after diagnosis.
- Favorable Safety Profile: The vaccine produced no serious adverse events and was given alongside standard post-operative recovery, radiation, and other care.
Source: WUSTL
Overview: A personalized vaccine designed to treat glioblastoma — a fast-growing brain cancer affecting about four in 100,000 people in the U.S. — proved safe and stimulated strong, tumor-specific immune responses in an early-phase clinical trial co-led by Washington University School of Medicine in St. Louis. In a subgroup of patients, immune activation correlated with improved recurrence-free survival following surgery.
In those with the particularly treatment-resistant unmethylated MGMT subtype, GNOS-PV01 showed no serious side effects and was associated with longer overall survival compared with historical outcomes after standard surgery and chemo-radiotherapy. One patient remains disease-free nearly five years after diagnosis.
The phase 1 GT-20 trial was conducted at Siteman Cancer Center (Barnes-Jewish Hospital/WashU Medicine) and the results were published May 12 in Nature Cancer. The study was led by Mass General Brigham and Geneos Therapeutics.
“We are very encouraged by these results,” said Tanner M. Johanns, MD, PhD, lead author and assistant professor in the Division of Oncology at WashU Medicine. He highlighted the potential of this individualized DNA vaccine platform and noted ongoing work at WashU to test combination strategies that might further improve outcomes.
The vaccine uses synthetic DNA constructs engineered to prompt the patient’s immune system to recognize proteins unique to that individual’s tumor. Those unique proteins, or neoantigens, are discovered by sequencing the tumor and selecting targets that can best stimulate an immune response.
Previous glioblastoma immunotherapies have sometimes provoked responses but failed to prevent recurrence, in part because tumors can rapidly evolve and shed targeted proteins. The GNOS-PV01 approach aims to overcome that by targeting many different neoantigens simultaneously, so loss of a few targets is less likely to allow immune escape.
In addition, the vaccine appears to remodel the tumor microenvironment from “cold” to “hot,” improving immune cell infiltration and activity within the tumor and increasing the likelihood of immune-mediated tumor clearance.
“We used a DNA platform because it lets us address a larger set of cancer proteins than prior vaccines could,” Johanns said. The platform induced immune responses against up to 40 neoantigens per patient — twice the number targeted in prior vaccine studies — increasing the chances of a clinically meaningful effect.
More targets, more chances for success
GNOS-PV01 is a multivalent vaccine targeting neoantigens—patient-specific tumor proteins that can be recognized by T cells. Neoantigen selection relied on computational algorithms developed at WashU Medicine by Obi Griffith, PhD, and Malachi Griffith, PhD. By choosing neoantigens from multiple tumor regions, the team increased the vaccine’s breadth of coverage.
The trial enrolled nine adults newly diagnosed with glioblastoma, all treated at Siteman Cancer Center. For each participant, researchers designed a synthetic DNA molecule encoding that patient’s set of neoantigens. Manufacturing occurred at the Biologic Therapy Core Facility at Siteman during post-operative recovery and radiation.
Vaccinations began on average 10 weeks after surgery, then continued every three weeks for nine weeks and subsequently every nine weeks as patients remained eligible. All but one participant—who required an immune-suppressing steroid—showed increased immune-cell activity after vaccination.
Two-thirds of patients were progression-free at six months and alive at one year, versus about 40% historically. One-third survived at two years. Median progression-free survival was 8.5 months and median overall survival was 16.3 months. One patient remains alive and recurrence-free almost five years after initial surgery.
An investment in the future
The report includes patient stories that illustrate the potential impact of the therapy. Kim Garland, a retired school nurse from Kirkwood, Missouri, was diagnosed at age 62 after a scan revealed a large brain mass. Following surgery at WashU Medicine and enrollment in the trial, she remains recurrence-free nearly five years later.
Kim and her husband Scott describe the trial experience as life-changing, allowing them to plan for the future and spend more time with family. Their story underscores the emotional as well as clinical importance of advances that extend survival and improve quality of life.
“Personalized neoantigen vaccines are an especially promising strategy for glioblastoma and other cancers,” said co-senior author Gavin Dunn, MD, PhD. He noted that such programs require close, multidisciplinary collaboration across medicine, surgery, computational biology, and manufacturing.
All participants in this study had unmethylated MGMT glioblastoma, a subtype that responds poorly to standard chemotherapy. The investigators plan to test GNOS-PV01 in larger trials and across a broader range of glioblastoma subtypes with the aim of improving response rates for more patients.
While hopeful, the Garlands still approach follow-up appointments with caution, recognizing the possibility of recurrence. They also take comfort in contributing to research that they hope will make a later diagnosis less frightening for others.
Funding: This study was supported by the Mark Foundation for Cancer Research Momentum Fellowship; NIH/NINDS grants R01NS117149, R01NS107833, and R01NS112712; the Nationwide Foundation Pediatric Innovation Fund; NIH K12CA167540; The Alvin J. Siteman Cancer Center Investment Program and The Foundation for Barnes-Jewish Hospital; The Schnuck Family Fund; The Knight and Christopher Davidson Family Fund; and additional support for development, manufacture, and monitoring from Geneos Therapeutics. The content remains the authors’ responsibility and does not necessarily represent the official views of the NIH.
R.P.L., J.Y., N.C., A.P.P., S.R., J.P., and N.Y.S are current or former employees of Geneos Therapeutics.
Key Questions Answered:
A: Scientists sequence the patient’s tumor to find unique proteins called neoantigens. Using computational tools, they select up to 40 targets and design a synthetic DNA construct that trains the patient’s immune cells to recognize and attack tumor cells presenting those neoantigens.
A: Glioblastoma often creates a suppressed, “cold” immune environment and evolves rapidly. Treatments that target only a few proteins can be evaded when the tumor stops producing those proteins. Broad neoantigen targeting aims to reduce that risk.
A: This trial focused on unmethylated MGMT glioblastoma, a subtype that typically resists chemotherapy. The next research steps will test GNOS-PV01 in a larger and more diverse glioblastoma population.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full.
- Additional context was added by our staff.
About this brain cancer research news
Author: Mark Reynolds
Source: WUSTL
Contact: Mark Reynolds – WUSTL
Image: The image is credited to Neuroscience News
Original Research: Open access. “Adjuvant personalized multivalent neoantigen DNA vaccination induces tumor-specific immune responses in newly diagnosed glioblastoma patients” by Garfinkle EA R, Perales-Linares R, Gimple RC, et al., 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 roughly 12–18 months. Neoantigen vaccines have shown promise in generating tumor-directed immune responses, but overall immunogenicity has been limited. This open-label, single-arm phase 1 trial (GT-20) evaluated the safety and feasibility of GNOS-PV01, a DNA-based personalized vaccine given after surgical resection and radiation for patients with unmethylated MGMT glioblastoma. Secondary endpoints included immunogenicity and preliminary clinical activity.
Nine patients were vaccinated with up to 40 neoantigens each (range 17–40). No serious adverse events or dose-limiting toxicities were reported. The vaccine induced activation and expansion of circulating T cells in all evaluated patients except one receiving dexamethasone. Six-month progression-free survival and 12-month overall survival were each observed in 66.7% of patients. Median progression-free survival was 8.5 months, median overall survival 16.3 months, and 24-month survival was 33%, including one long-term survivor still alive approximately four years after initial surgery. The study met its pre-specified endpoints and supports further evaluation of GNOS-PV01 as part of glioblastoma immunotherapy. ClinicalTrials.gov identifier: NCT04015700.