mRNA vaccination using peptide nanoparticles triggers a strong immune response against endogenous GPC2 in a murine...

Neuroblastoma is an aggressive pediatric solid tumor that arises during embryonic development and contributes to 15% of cancer-related deaths in children. To date, neither experimental nor clinical trial data on an mRNA vaccine for neuroblastoma have been published, highlighting a significant gap in the anticancer vaccine development pipeline. This study presents the first mRNA vaccine for the treatment of neuroblastoma. We explored the self-assembling peptide RALA for delivering mRNA encoding glypican 2 (GPC2), a potent tumor-associated antigen in neuroblastoma. These data outline rigorous in vitro characterization of vaccine nanoparticle formulations, cellular uptake, and functionality. Immunization of mice with RALA/mGPC2 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. Immunization delayed tumor development by 10-11 days and reduced tumor volume by 70% compared with unvaccinated controls in a subcutaneous murine model of MYCN-amplified neuroblastoma. This work demonstrates the therapeutic potential of the RALA/mGPC2 vaccine for treating neuroblastoma. Additionally, GPC2 is upregulated across multiple adult and pediatric cancer subtypes, establishing this vaccine as an attractive immunotherapy with far-reaching potential.