Development of a mRNA vaccine for prostate cancer

Through bioinformatics methods, the consensus sequences of dendritic cell-associated proteins were identified, thereby enabling the construction of dendritic cell-targeting CPPs, HAWC. HAWC is a 24 AA and able to condense mRNA into ideal. Furthermore, transfection efficiency was found up to 80% in the DC 2.4, NCTC-929s and RM-1 cell lines, with no detectable toxicity.

Moreover, in vivo biodistribution studies were shown that HAWC NPs was expressed in the spleen and lungs, which were dendritic cell-rich organs, and was specifically internalised by cDC1, cDC2, macrophages, and leukocytes.<br><br>Additionally, bioinformatics analysis identified two tumour-associated antigens (PRAME and PSMA) for prostate cancer. Immunological studies showed that vaccinated mice have a higher CD4+ and CD8+ T -cell response than unvaccinated mice.

Therapeutic studies have shown that vaccinated mice have a significant delay in tumour progression during the early stage compared to unvaccinated in RM-1 prostate cancer model. These findings showed that the consensus sequence-based targeted delivery platform has been successfully developed and validated within this thesis. This study expands targeted delivery methodologies and demonstrates proof of concept for targeted delivery to other cells/tissues.<br><br><i>Thesis is embargoed until 31 July 2031.</i>