Developing a neoantigen-like, ROP-based vaccine targeting SVN (ROP-SVN) to boost host immune responses
Primary Supervisor: Professor Shisong Jiang
Second Supervisor: Professor Eric O'Neill
Project Overview
Tumour-associated antigens (TAAs) are prevalent in cancer cells and are potential targets for cancer vaccines. However, tumour cells employ mechanisms to hinder TAA presentation internally, evading T cell recognition and killing. TAAs are often viewed as self-antigens by the host, leading to reduced immunogenicity when used in vaccines. Furthermore, wildtype-TAAs (WT-TAAs) are oncoproteins and tumourigenic, rendering them unsuitable for direct use in cancer vaccines. We aim to address these challenges by developing recombinant overlapping peptides (ROP)-based cancer vaccines to bolster host immunity. ROPs rearrange WT-TAA sequences to preserve T and B cell epitopes while abolishing the conformation and functions of oncoproteins, effectively transforming a WT-TAA into a safer and more immunogenic, neoantigen-like vaccine. Our goal is to develop mRNA-based ROP vaccines, offering advantages such as easy manufacturing and fewer hurdles for protein purification and refolding. We will evaluate their efficacy compared to protein-based counterparts. Additionally, we will assess the combination of other immunotherapies with ROP-based vaccines, aiming to optimise the cancer therapeutic strategy.
Training Opportunities
This project provides outstanding training opportunities, equipping the DPhil student with a broad skill set in advanced research methodologies. The student will gain expertise in mRNA vaccine technology, including the design and synthesis of recombinant overlapping peptides (ROP) and their formulation into lipid nanoparticles (LNPs) through collaborations with experienced partners. These skills are crucial for driving innovation in cancer immunotherapy. In vitro training will include conducting antigen presentation studies using advanced cell lines and employing techniques such as ELISPOT and flow cytometry to evaluate immune responses. The project also offers the opportunity to explore combination therapies with immune-oncology agents, providing a comprehensive understanding of their synergistic mechanisms. By engaging in multidisciplinary collaborations and cutting-edge research, the student will be well-prepared to lead future innovations in cancer immunotherapy, contributing to the development of transformative treatments with strong translational and clinical potential.
Relevant Publications