Development of a saRNA nano-vaccine for Prostate Cancer

Treatment options for castrate resistant prostate cancer (CRPC) are primarily palliative. Clinically relevant immune-cell stimulated tumour-associated antigens (TAAs) have been identified that negatively correlate with treatment outcome. Nucleic acid vaccination holds tremendous potential, possessing both prophylactic and therapeutic application. Of these, RNA vaccines are much more potent than DNA vaccines, with smaller quantities stimulating greater immune responses. RNA-based vaccines have the advantage of low manufacturing cost, inducing B and T cell responses, high specificity, high stability, absence of anti-vector immunity, lower reactogenicity and lacking the ability to be integrated into the host cells genome. The main disadvantage of using RNA as a vaccine is the requirement for cytoplasmic delivery to host cells and generating a strong long-lasting immunity. This project is designed to overcome these limitations by using our patented non-immunogenic drug delivery system (RALA) to improve cytoplasmic delivery and to enhance the immune response by delivering both saRNA encoding TAAs for CRPC and B cell activating CpG adjuvants. The end-point will determination of a candidate RALA/saRNA vaccine that will elicit both prophylactic and therapeutic immune responses to CRPC tumours that can then be further developed towards the clinic.

This projects forms part of an exciting collaborative partnership between Professor McCarthy, a nucleic acids drug delivery expert and CEO of Phion Therapeutics and Dr Jonathan Coulter, a prostate cancer expert in translational medicine. The student will benefit from training in both an academic and industry setting including placements in Phion Therapeutics. The project workplan encompasses a broad range of molecular biology, physiochemical and in vivo techniques providing the student with an excellent training environment and key transferable skills for future development.