First Preclinical mRNA Vaccine for Neuroblastoma Shrinks Tumors by 70% in Murine Models
核心洞察
RCSI researchers have published the first preclinical proof-of-concept for an mRNA vaccine targeting neuroblastoma (搜索), the deadliest childhood cancer.
The vaccine, delivered via self-assembling peptide nanoparticles targeting Glypican 2 (GPC2) (搜索), reduced tumor volume by 70% and delayed tumor development by 10–11 days in murine models.
Neuroblastoma (搜索) accounts for 15% of all pediatric cancer deaths, and 80% of high-risk patients show no significant response to current standard therapies.
A new study from RCSI University of Medicine and Health Sciences (搜索) has delivered the world's first preclinical proof-of-concept for an mRNA vaccine targeting neuroblastoma (搜索), the deadliest form of childhood cancer. Published in Molecular Therapy Oncology, the research demonstrates that an mRNA vaccine delivered via self-assembling peptide nanoparticles can train the immune system to recognize and attack neuroblastoma cells, achieving a 70% reduction in tumor volume and delaying tumor development by 10 to 11 days in a subcutaneous murine model of MYCN-amplified neuroblastoma.
The study, led by Dr. Olga Piskareva, Senior Lecturer in the RCSI Department of Anatomy and Regenerative Medicine, addresses a significant gap in the anticancer vaccine development pipeline. "To date, neither experimental nor clinical trial data on an mRNA vaccine for neuroblastoma (搜索) have been published," the authors note in their paper, underscoring the novelty of this approach.
A High-Stakes Target in Pediatric Oncology
Neuroblastoma (搜索) is an aggressive pediatric solid tumor that arises during embryonic development and contributes to 15% of cancer-related deaths in children. Despite advances in therapy, it remains a leading cause of childhood cancer deaths. Between five and ten cases are diagnosed in Ireland each year, with 80% of patients showing no significant response to current treatments. Neuroblastoma that recurs after initial treatment is particularly difficult to cure, as the cancer often becomes resistant to existing therapies.
Peptide Nanoparticle Delivery and GPC2 Targeting
The researchers employed a novel delivery platform based on the self-assembling peptide RALA to transport mRNA encoding Glypican 2 (GPC2) (搜索), a potent tumor-associated antigen heavily expressed on the surface of neuroblastoma (搜索) cells. These peptide nanoparticles form tiny self-assembling particles designed to deliver the mRNA payload directly to target sites, where it instructs host cells to produce the GPC2 antigen and trigger an immune response.
Rigorous in vitro characterization of vaccine nanoparticle formulations, cellular uptake, and functionality preceded the in vivo experiments. Immunization of mice with the RALA/mGPC2 vaccine generated an antigen-specific cellular immune response against GPC2, with significant increases in IFN-γ and IL-2 expression by splenocytes and TNF-α expression by CD4+ and CD8+ T cells.
Modular Design and Broader Implications
Dr. Piskareva described the vaccine's architecture in accessible terms: "The mRNA vaccine technology is like LEGO bricks. By combining different bricks, we can tailor the vaccine to the individual needs with high precision. This pilot study indicates promising potential in the development of anticancer vaccines for neuroblastoma (搜索), offering new hope for children and families suffering from the disease. We are at the beginning of the mRNA vaccine development road, but the first milestone has been successfully completed."
Importantly, GPC2 is upregulated across multiple adult and pediatric cancer subtypes, establishing this vaccine as an attractive immunotherapy with far-reaching potential beyond neuroblastoma (搜索). The modular nature of the platform further supports adaptation to other tumor types.
Collaboration and Funding
The study was carried out in collaboration with the School of Pharmacy at Queen's University of Belfast and was funded by the Irish Research Council (IRC), the Higher Education Authority (HEA), the Health Research Board (HRB), and The Conor Foley Neuroblastoma (搜索) Cancer Research Foundation. The full paper is published open access in Molecular Therapy Oncology (DOI: 10.1016/j.omton.2026.201244).