Close
Enter your
text here

Phase I Glioblastoma Cancer Vaccine Trial Shows Promise for Patients and Novel Vaccine Platform

Phase I Glioblastoma Cancer Vaccine Trial Shows Promise for Patients and Novel Vaccine Platform 1024 683 Katie Brind'Amour, PhD, MS, CHES
Close up of gloved doctor's hands injecting vaccine medicine into a syringe - stock image

Early results suggest extended survival and the potential to manufacture customized vaccines that target up to 40 patient-specific neoantigens.

Glioblastoma is the most common primary central nervous system cancer in adults. Highly heterogenous from patient to patient and even within a single tumor, it is notoriously hard to treat — especially for a subgroup of patients in whom chemotherapy is not beneficial, those with unmethylated MGMT glioblastoma. Historically, median survival for these patients is 12-18 months, and only 10-15% of patients survive to 24 months after diagnosis. Now, a Phase I study demonstrates that experimental DNA vaccines targeting up to 40 patient-specific tumor antigens have a low side effect profile and suggests this approach may hold promise for extending life in patients with this aggressive disease.

“At the time the study was designed, it was the first cancer vaccine to include up to 40 neoantigens,” says Elizabeth Garfinkle, PhD, research scientist in the Steve and Cindy Rasmussen Institute for Genomic Medicine (IGM) at Nationwide Children’s Hospital and lead author on a Nature Cancer paper detailing the study’s results. “We’ve shown that we can predict and include many of the expressed tumor-specific mutations that are likely to stimulate an immune response in a given patient, while still maintaining a favorable safety profile.”

For the trial, led by investigators at Washington University in St. Louis, each enrolled patient had tumor resection and radiotherapy according to standard care practices. Post-operative biopsies were then sent to the team at IGM for molecular profiling and neoantigen identification.

“We received multisector samples from each tumor and co-extracted the DNA and RNA. The DNA was profiled to identify abnormal genes, and the RNA showed us which of those mutations were expressed,” says Dr. Garfinkle. “We then used an algorithm trained to predict which neoantigens are most likely to be immunogenic (to stimulate a T cell response) in each patient. That information was sent back to our collaborators at Washington University, who used it to prioritize which neoantigens would go into each participant’s vaccine.”

Of the nine participants, personalized vaccines were produced with a median of 36 (range: 17-40) neoantigens per vaccine. The participants had no targeted antigens in common. Once the vaccines were manufactured, participants received priming doses every 3 weeks for 9 weeks followed by boosters every 9 weeks thereafter. Participants received a median of 4 doses (range: 2-18), and no one experienced unexpected toxicities or stopped vaccination due to adverse events. Three participants experienced disease progression after surgery and radiation but before receiving their first vaccine.

Median survival was 16.3 months. One-third (n=3) of participants were alive at 24 months, one of whom has survived 4 years post-surgery. Median progression-free survival was 8.5 months, and two-thirds (n=6) of all patients were alive 12 months post-surgery.

For participants requiring a second resection after cancer progression, the team had an opportunity to re-analyze post-vaccine tumor samples to study what changes had occurred since vaccination. This enabled IGM researchers to identify immune responses resulting from the vaccine, which could inform future work in neoantigen selection or vaccine dosing schedules.

“This Phase 1 study indicates that personalized vaccines are well tolerated and stimulate the patient’s immune system to attack the glioblastoma cells in a highly specific manner,” says Elaine Mardis, PhD, co-executive director of IGM at Nationwide Children’s and a long-term collaborator with the clinical team at Washington University. Dr. Mardis is currently serving on a vaccine advisory panel for the National Cancer Institute that is working to define the most promising approaches to anti-cancer vaccines and corresponding clinical trial designs.

The glioblastoma study highlighted the necessity of swift vaccine development as essential to the design of such trials, as multiple participants had progressive disease before their first vaccination. Median time to develop the vaccine after surgery was 22 weeks.

“With this study we encountered some pain points in vaccine turnaround — the goal was to get everyone vaccinated within 4 weeks of completing their 6-week radiotherapy course,” says Dr. Garfinkle. “But as we increase the number of neoantigens included, the complexity and time required for manufacturing also increases. There’s a balance between designing a highly personalized, comprehensive vaccine and being able to deliver it quickly enough for individuals with aggressive disease.”

The team of clinical investigators have a larger study now underway in which customized vaccines will be paired with checkpoint inhibitor therapy in an effort to evaluate toxicity and adverse events, and whether this combination therapy enhances treatment effects. To shorten the time between surgery and first vaccination, the Washington University team will manufacture the new trial’s vaccines in-house after analyzing each participant’s prioritized neoantigen profile from the IGM team.

Dr. Garfinkle is optimistic about the broader implications of this approach.

“It’s exciting to think we actually helped participants just by looking at their genome,” she says. “Being able to contribute that level of insight into an individual’s tumor and then see evidence that the vaccine is activating their immune system feels like a meaningful step toward improving outcomes for glioblastoma and other cancers.”

 

Reference: 

Garfinkle EAR, Perales-Linares R, Gimple RC, Livingstone AJ, Roberts KF, Butt OH, Goedegebuure SP, McLellan MD, Chang GS, Hundal J, Yan J, Navarro JB, Paxton SA, Chattopadhyay S, Cooch N, Perales-Puchalt A, Stavroulaki K, Rochestie S, Peters J, Junker B, Campian JL, Chheda MG, Chicoine MR, Kim AH, Willie JT, Zipfel GJ, Dowling JL, Miller CA, Griffith OL, Griffith M, Gillanders WE, Miller KE, Mardis ER, Sardesai NY, Dunn GP, Johanns TM. Adjuvant personalized multivalent neoantigen DNA vaccination for MGMT unmethylated glioblastoma: a phase I trial. Nature Cancer, 12 May 2026.

 

Image Credit: Adobe Stock

About the author

Katherine (Katie) Brind’Amour is a freelance medical and health science writer based in Pennsylvania. She has written about nearly every therapeutic area for patients, doctors and the general public. Dr. Brind’Amour specializes in health literacy and patient education. She completed her BS and MS degrees in Biology at Arizona State University and her PhD in Health Services Management and Policy at The Ohio State University. She is a Certified Health Education Specialist and is interested in health promotion via health programs and the communication of medical information.

You might also like