Brain Metastasis Treatment in China: Nose-to-Brain Immunotherapy Delivery Published in Science Advances

Brain Metastasis Treatment in China: A New Delivery Method for Immunotherapy

For patients and families facing a diagnosis of melanoma brain metastases, the challenge is twofold: the cancer has spread to a place where many drugs cannot reach, and the tumor itself creates a hostile environment that suppresses the immune system. A new study from Southeast University in China, published in the journal Science Advances, reports a non-invasive method to deliver immunotherapy directly to the brain, potentially overcoming these barriers. The research focuses on a nose-to-brain delivery platform that could change how brain metastasis treatment in China is approached.

The Problem: Blood-Brain Barrier and Immune Evasion

Melanoma brain metastases are the third most common type of intracranial metastatic tumor, associated with high rates of disability and death. The blood-brain barrier, while essential for protecting the brain, severely limits the penetration of large-molecule antibody drugs, making traditional intravenous administration largely ineffective. Inside the tumor microenvironment, two specific mechanisms further complicate treatment. The CD73/adenosine axis promotes immune escape, while IL-17 drives the HIF-1α/VEGF-A signaling pathway, intensifying immunosuppression. Together, these factors have been a critical bottleneck for CD73-targeted immunotherapy.

The Innovation: A Glycerol-Mediated Nose-to-Brain Platform

Researchers led by Professor Jinbing Xie at the School of Medicine, Southeast University, developed a non-invasive intranasal delivery system using glycerol, a biocompatible compound, as a mucosal permeation enhancer. The study, titled “Glycerol-mediated nose-to-brain codelivery of anti–IL-17 and anti-CD73 antibodies enhances immunotherapy for melanoma brain metastases,” demonstrates that a 5% glycerol solution can reversibly open tight junction proteins in the nasal mucosal epithelium. This allows for enhanced delivery of anti-IL-17 and anti-CD73 antibodies directly to the brain while significantly reducing systemic drug exposure and the off-target toxicity common with traditional methods.

How the Combined Therapy Works

The co-delivery strategy does more than just get drugs into the brain. Once there, it actively remodels the tumor immune microenvironment. The research showed a marked increase in the activation and infiltration of CD8+ cytotoxic T cells, a shift in macrophages toward an anti-tumor phenotype, and a reduction in immunosuppressive regulatory T cells (Tregs). In animal models of melanoma brain metastases, this approach achieved a potent anti-tumor effect. The study proposes a new treatment paradigm: targeting IL-17 to break through the tumor microenvironment’s restriction on CD73-targeted immunotherapy.

This platform is not limited to melanoma. The researchers note its potential application for primary intracranial tumors like glioblastoma and brain metastases from other malignant cancers. For those exploring brain tumor treatment options in China, this represents a significant scientific advance. The study was supported by the National Natural Science Foundation of China, the National Key Research and Development Program, and the Jiangsu Provincial Innovation and Entrepreneurship Team Program. Co-first authors are doctoral students Xuhong Yang and Nuo Xu, along with Associate Researcher Hui Yang. Professors Jinbing Xie and Yicheng Ni are co-corresponding authors.

Source: 东南大学医学院