Intranasal peptide nanovaccine achieves 43% complete glioblastoma regression by bypassing blood-brain barrier | Research

The takeaway

Survivin peptide-CpG nanovaccines administered sequentially via intranasal and IV routes achieved 43% complete glioblastoma regression in mice by bypassing the blood-brain barrier through olfactory and trigeminal nerve pathways.

43% complete regression
Intranasal peptide nanovaccine bypassed the blood-brain barrier to achieve remarkable complete glioblastoma regression rates in mice

What the researchers found

Sequential intranasal/IV administration with anti-CTLA-4: 43% complete GBM regression. Intranasal route bypassed BBB via olfactory bulb and trigeminal nerve. Enhanced DC uptake and activation. Robust local and systemic anti-GBM immunity.

Why it matters

GBM is virtually incurable with <8 months median survival. A nasal spray vaccine that delivers immunotherapy directly to brain tumors could revolutionize treatment by overcoming the blood-brain barrier—the main obstacle to effective brain cancer therapy.

How the study worked

Nanovaccine synthesis (survivin peptide-CpG polymersomes), in vitro BBB penetration and DC activation, orthotopic murine GL261 GBM model, biodistribution imaging, combination with anti-CTLA-4.

What this study cannot tell us

Mouse model only (GL261). Single tumor model tested. Combination with checkpoint inhibitor needed for optimal efficacy. Human BBB anatomy may differ. Scalability and GMP manufacturing undefined.

How to read the evidence

Preclinical with orthotopic brain tumor model—strong proof of concept. Impressive regression rates but mouse-only data.

When this study was published

Published in 2025.

The bigger picture

Intranasal vaccine delivery to brain tumors is a paradigm-shifting approach. If translatable to humans, this strategy could address not only GBM but potentially other brain malignancies and neurological diseases requiring brain-targeted immunotherapy.

Questions still open

Will intranasal delivery work similarly in human brain tumor patients?
Can the platform be adapted for other brain tumor antigens?
Is the 43% regression rate durable long-term?

Common questions

How does a nasal spray treat brain cancer?

The nanovaccine travels from the nose to the brain through nerve pathways (olfactory and trigeminal nerves), completely bypassing the blood-brain barrier that blocks most drugs. Once in the brain, it activates the immune system to attack the tumor using peptides from survivin, a protein found on cancer cells.

Could this cure glioblastoma?

In mice, the treatment achieved complete tumor elimination in 43% of cases. This is remarkable for glioblastoma, which is currently incurable. However, mouse results often do not fully translate to humans, and clinical trials are needed to determine if the approach works in people.

Read the original research

Intranasal and Intravenous Sequential Administration of Survivin Peptide-CpG Nanovaccines Elicits Potent Immunity Toward Glioblastoma.

Advanced materials (Deerfield Beach, Fla.), 37(33), e2420630

View on PubMed ↗Publisher’s paper ↗

Citation

Shi, Yan; Sun, Yinping; Zhao, Songsong; Sun, Zhiwei; Xia, Mingyu; Zhong, Zhiyuan; Meng, Fenghua. (2025). Intranasal and Intravenous Sequential Administration of Survivin Peptide-CpG Nanovaccines Elicits Potent Immunity Toward Glioblastoma.. Advanced materials (Deerfield Beach, Fla.), 37(33), e2420630. https://doi.org/10.1002/adma.202420630