Development of mRNA Vaccines for Children with High-Risk Neuroblastoma

Neuroblastoma is one of the most aggressive childhood cancers contributing to 15% of cancer related childhood deaths. At diagnosis half of the patients have a metastatic tumour and recurrence is very common. Despite advances in available therapies, children with drug-resistant and relapsed neuroblastoma have a dismal outlook with 5-year survival rates of less than 20%, highlighting the need for new treatments. Immunotherapies, including anti-tumour vaccines, hold great promise to effectively target the tumour while generating fewer side effects and associated toxicities. This is achieved through the mechanism of action of vaccines that teach the immune system to identify and combat the tumour offering long-term protection against recurrence. It is also forecasted that the success of COVID-19 messenger ribonucleic acid (mRNA) vaccines is set to boost the therapeutic oligonucleotide market to reach $4.5B by 2027 globally. This project aims to develop the first mRNA vaccine against high-risk neuroblastoma. Specifically, we will select two well characterised neuroblastoma cell surface antigens to be targeted in a mRNA vaccine. This vaccine will be delivered using RALA peptide, based on previous studies of the applicant team. The RALA/mRNA nanoparticles will be characterized for shape, surface charge, stability and immunogenicity. The transfection efficiency of the vaccine will be determined in vitro using DC 2.4 cells (murine dendritic cell line) and in THP-1 cells (human monocytic cell line). For the immunogenicity studies, C57 BL/6 mice will receive the vaccine and blood samples will be collected to analyse specific antibodies and cytokine secretion. The therapeutic and prophylactic potential of RALA/mRNA vaccine will be analysed using a metastatic model of neuroblastoma and a PDX humanized mouse model. Finally, we will evaluate the regulatory options to ensure an efficient therapy translation to the clinical setting. This will include market analysis as well as intellectual property and orphan drug designation applications.

Award Date
18 November 2022
Award Value
Principal Investigator
Dr Olga Piskareva
Host Institution
HRCI-HRB Joint Funding Scheme