Virus-like particle vaccine targeting meningeal lymphatic vessels via intradural delivery activates anti-glioma immunity.

BACKGROUND

Glioblastoma (GBM) is a lethal brain tumor with a poor prognosis, largely due to an immunosuppressive microenvironment and the blood-brain barrier. The discovery of meningeal lymphatic vessels (MLVs) offers a new avenue for central nervous system immune engagement.

OBJECTIVE

We aimed to develop a novel immunotherapy by combining a virus-like particle (VLP) nanovaccine with intradural administration to activate meningeal immunity against GBM.

METHODS

A virus-like particle (VLP)-based nanovaccine (OVA-HBc) was engineered and characterized. Its efficacy was evaluated in an orthotopic GL261-OVA-Luc glioma mouse model, comparing intradural delivery with intravenous and intranasal routes through tumor imaging and survival analysis.

RESULTS

OVA-HBc formed stable nanoparticles (~ 36 nm), was non-toxic, and potently activated dendritic cells in vitro. In vivo, only intradural administration of OVA-HBc induced marked tumor regression and was associated with prolonged survival (over 60% survival at 60 days), showing potential advantages over systemic routes. This effect is likely mediated by precise meningeal targeting and efficient antigen drainage via MLVs.

CONCLUSION

This study suggests that intradural delivery of HBc VLPs can engage MLVs to activate anti-glioma immunity in a mouse model. This approach offers a potential strategy to bypass certain central delivery barriers, representing a preliminary framework for GBM immunotherapy.