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

Neuroblastoma is an aggressive pediatric solid tumor that arises during embryonic development and contributes to 15% of cancer-related deaths in children. Four out of five patients with clinically aggressive disease do not show sustained responses to recent advances in anticancer therapy, thus highlighting the urgent need for novel treatments. We explored the ability of the self-assembling peptide RALA to deliver mRNA encoding glypican 2 (GPC2), a potent tumor-associated antigen in neuroblastoma. This study presents the first RALA/mGPC2 vaccine for the treatment of neuroblastoma. The RALA/mGPC2 nanoparticles were characterized with respect to the optimal formulation, cellular uptake and functionality. Compared with the control, the immunization of mice with RALA/mGPC2 generated a potent cellular immune response against the encoded GPC2, delayed the time until tumor development by 10-11 days and significantly lowered the tumor burden. Thus, the tumor volume of vaccinated animals was reduced by 70%. This work demonstrated the therapeutic potential of the RALA/mGPC2 vaccine for treating neuroblastoma. While this study focused on neuroblastoma, GPC2 is upregulated in multiple cancer subtypes, making the RALA/mGPC2 vaccine an attractive immunotherapy beyond its original application.