University of Macau Unveils Groundbreaking Ferritin-Based Vaccine for Brain Cancer

The University of Macau (UM) has achieved a significant milestone in oncology research with the development of a novel ferritin-based photoimmunotherapeutic in situ vaccine, known as FIT, targeting glioblastoma (GBM) and brain metastases (BM). Published in the prestigious journal Cell Biomaterials on February 18, 2026, this innovation addresses two major hurdles in brain cancer treatment: the blood-brain barrier (BBB), which blocks most drugs and immune cells from reaching tumors, and the immunosuppressive tumor microenvironment that evades standard therapies.

Led by Professor Zhen Yuan from UM's Faculty of Health Sciences (FHS) and Centre for Cognitive and Brain Sciences (CCBS), the study demonstrates how FIT leverages natural lymphatic pathways for precise delivery, achieving over 50% long-term survival in preclinical mouse models of orthotopic GBM and BM with no observable toxicity. This positions UM as a leader in precision oncology within China's higher education landscape.

Understanding Glioblastoma: The Lethal Brain Cancer Challenging Modern Medicine

Glioblastoma multiforme (GBM), a grade IV glioma, is the most aggressive primary brain tumor, accounting for approximately 50% of all malignant brain tumors. In China, brain and central nervous system (CNS) cancers rank among the top causes of cancer-related deaths, with an age-standardized incidence rate of about 4.1 per 100,000 and mortality of 3.2 per 100,000. Despite multimodal treatments including surgery, radiotherapy, and temozolomide chemotherapy, the median survival is merely 12-15 months, with 5-year survival rates hovering around 5-17%—even lower for recurrent cases or brain metastases from lung, breast, or melanoma primaries.

The BBB, a protective layer of endothelial cells, astrocytes, and pericytes, prevents 98% of small molecules and nearly all immune cells from penetrating the tumor site. Coupled with GBM's ability to recruit immunosuppressive cells like myeloid-derived suppressor cells and M2 macrophages, this creates an 'immune-cold' environment resistant to immunotherapies like checkpoint inhibitors. For patients in Macau and mainland China, where incidence is rising due to aging populations, innovative solutions are urgently needed.

The FIT Vaccine: Harnessing Ferritin Nanocages for Targeted Brain Delivery

FIT, or ferritin-based photoimmunotherapeutic in situ vaccine, utilizes human heavy-chain ferritin (HFn), a natural 24-subunit nanocage protein (12 nm diameter), renowned for its biocompatibility and tumor-targeting via transferrin receptor 1 (TfR1) overexpression on GBM cells. The nanocage encapsulates a Toll-like receptor 7/8 (TLR7/8) agonist, T785, in its core through pH-responsive disassembly/reassembly, while surface-adsorbing indocyanine green (ICG), an FDA-approved near-infrared (NIR) photosensitizer.

Unlike traditional vaccines requiring direct tumor injection, FIT is administered subcutaneously in the neck, draining to deep cervical lymph nodes (dCLNs). Here, it 'piggybacks' on pre-dendritic cells (pre-DCs), which internalize it as a Trojan horse. Acidic endolysosomes trigger T785 release, activating DCs to mature and migrate via meningeal lymphatic vessels (MLVs)—recently discovered drainage pathways from brain to periphery—directly into the tumor.

Step-by-Step Mechanism: From Injection to Systemic Immunity

The FIT mechanism unfolds in precise stages:

• Step 1: Lymphatic Targeting Subcutaneous injection leads FIT to dCLNs, where TfR1-mediated uptake by pre-DCs occurs.
• Step 2: pH-Responsive Activation In acidic compartments (pH 5.5), ferritin disassembles, releasing T785 to stimulate TLR7/8, promoting DC maturation and antigen presentation.
• Step 3: Trojan Horse Migration Primed DCs traffic via MLVs into the brain tumor, bypassing BBB.
• Step 4: Phototherapy Ignition NIR laser (808 nm) activates ICG for photothermal (heat) and photodynamic (reactive oxygen species) effects, inducing pyroptotic tumor cell death and antigen release.
• Step 5: Adaptive Immunity Amplification Released antigens drain back to dCLNs, priming T cells and B cells for systemic, memory-driven antitumor response, remodeling the tumor microenvironment from cold to hot.

This closed-loop lymphatic-tumor crosstalk ensures sustained immunity.

Preclinical Triumph: Over 50% Survival in Aggressive Mouse Models

In orthotopic GBM (GL261-luc) and BM (4T1-luc) syngeneic mouse models mimicking human disease, FIT + NIR achieved >50% long-term survival (beyond 90 days), compared to <10% for controls. Flow cytometry revealed increased CD8+ T cells and NK cells in tumors, with elevated IFN-γ and reduced Tregs. No weight loss or neuroinflammation observed, confirming safety. Synergy with anti-PD1 further boosted efficacy, suggesting combinability.

These results outperform systemic checkpoint inhibitors alone, highlighting lymphatic delivery's superiority.Read the full study in Cell Biomaterials

Photo by Muhammad Faiz Zulkeflee on Unsplash

UM Faculty of Health Sciences: A Hub for Brain Cancer Innovation

UM FHS, under Prof. Yuan's leadership, excels in optical theranostics and nanomedicine. Recent feats include scorpion venom peptide nanoparticles (G5C9) for GBM via PI3K/AKT inhibition and magnesium-phenolic nanoeditors repolarizing macrophages for enhanced CTL infiltration. Funded by Macao SAR FDCT, NSFC, and UM grants, these efforts underscore UM's role in Greater Bay Area biomedical research. Aspiring researchers can explore opportunities via higher ed jobs or AcademicJobs China.

Overcoming Traditional Barriers: Why FIT Stands Out

Ferritin nanocages excel due to self-assembly, biocompatibility, and TfR1 specificity, previously used in cancer vaccines but not for brain via lymphatics.

Implications for China: Addressing Rising Brain Cancer Burden

China projects 145,650 new brain/CNS cases by 2030, with GBM comprising half. Low survival (9-18% 5-year) demands localized innovations like FIT, potentially integrable with CAR-T or oncolytic viruses. Macau's strategic position accelerates clinical trials via Zhuhai UM Institute collaborations. For professionals, higher ed career advice on oncology research abounds.

Future Horizons: Toward Clinical Translation

FIT's subcutaneous administration and FDA-approved components (ferritin, ICG) facilitate Phase I trials. Challenges include human MLV variability and scalability, but UM's infrastructure supports GMP production. Combinatorial regimens could elevate survival beyond 70%. Prof. Yuan's team eyes CNS applications like Alzheimer's.

Stakeholder Perspectives and Broader Impact

Experts praise lymphatic targeting's elegance, echoing prior MLV studies enhancing RT/immunotherapy. Patients and oncologists in China anticipate reduced recurrence. UM bolsters STEM talent; visit university jobs for roles in FHS.

Photo by Mathew Schwartz on Unsplash

Call to Action: Join the Fight Against Brain Cancer

UM's FIT exemplifies Chinese universities' global impact. Researchers, rate professors at Rate My Professor, seek higher ed jobs, or explore career advice. Share insights in comments below.