Alexander Stephens

I graduated in 2012 with a Bsc. (Hons) Biochemistry degree from the University of Southampton. Up until 2019 I worked in the biotechnology sector, first as a Production technician in a company based near oxford producing viral and bacterial antigens, and secondly for a company based in Cambridge as a scientist in the cell line development group producing monoclonal antibodies. I joined the Jiang lab in 2019 as a Research Scientist working on a mucosal delivery platform for recombinant overlapping peptides before starting my DPhil later that year.

My Research focuses on recombinant overlapping peptides (ROPs) as a peptide cancer vaccine. ROPs  consist of short overlapping amino acid sequences formed into a single-chain peptide encompassing the sequence of a cancer antigen. Between each overlapping region is an enzymatic cleavage site specific for cleavage within the cytosol of dendritic cells (DC), the primary antigen presenting cell of the adaptive immune response.

Exogenous antigens are typically taken up by DCs and processed within endosomes for loading onto MHC Class II molecules for the presentation to CD4+ T-helper cells, in a process known as antigen presentation. CD4+ T-cell activation leads to release of cytokines and activation of macrophages and cytotoxic T-cells. A small proportion of exogenous antigens can escape from the endosomes and are processed in the cytosol by the proteasome, where they are loaded onto MHC class I molecules and presented to CD8+ cytotoxic T-cells, to initiate cell-mediated cytotoxicity. This process is known as antigen cross-presentation. For a robust anti-tumour response, activation of both CD4+ and CD8+ pathways are required for activation and maintenance of immunity against a cancer antigen, which ROPs can achieve through its ability to be efficiently presented by MHC class I and II molecules.

The aim of my project is to establish an optimised ROP expression and purification system, and to use ROPs to study the mechanisms of antigen cross-presentation, to inform the production of clinically relevant ROPs as an alternative cancer immunotherapy.