About
Research Interests
Prof Savelyeva has focused on the development of novel immunotherapeutic interventions for head and neck cancer and lung cancer. She has developed several immunotherapeutic approaches including a number of cancer vaccine platforms. Her long-standing interest is in DNA vaccines. Having worked on several plasmid DNA vaccines, her current interest lies in unconventional non-plasmid-based DNA vaccine platforms. Doggybone DNA is an innovative vaccine platform that utilizes a cell-free enzymatic process to amplify and DNA, resulting in a simplified structure that lacks bacterial sequences such as antibiotic resistance genes, The enzymatic manufacturing through a rolling circle amplification by Phi29 polymerase results in the generation of a linear closed-end DNA. This simple cassette can drive the antigen expression in vivo and induce robust cellular and humoral immune response. Prof Savelyeva’s research group is actively pursuing optimisation of doggybone DNA vaccines. Prof Savelyeva works closely with Prof Ottensmeier (University of Liverpool) to bring these novel, safe and efficacious candidate vaccines to the clinic. Prof Savelyeva enjoys collaborating with many industrial with the key partner being Touchlight Genetics (London)
Novel vaccines and clinical trials
Our novel vaccine candidate TGL-100 has been developed in collaboration with Cancer Research Malaysia and with our industrial partner Touchlight Genetics to utilise doggybone DNA technology. TGL-100 is targeting two novel antigens frequently expressed in a number of solid cancers including head and neck and lung cancers. These cancers have a high incidence in Liverpool and South East Asian countries including Malaysia. The vaccine aims to induce a robust cytotoxic T-cell response to destroy cancer cells. We are also addressing novel ways to facilitate the doggybone DNA delivery in patients. This will be first time doggybone DNA vaccines will be tested in patients.
Cancer antigens
We are interested in targeting both, antigens which are shared between patients and antigens which are expressed in individual patient cancers but not elsewhere in the body. We believe that both types of antigens are promising for targeting in cancer. TGL100 vaccine targets shared antigens. A personalised approach deals with the identification of mutations expressed by patients’ tumours, the “cancer mutanome” and we have focused on the developing of a robust pipeline for the identification of targetable epitopes. Our Neovacc trial will target individual patient’s mutanomes and will also use the doggybone DNA platform to deliver antigen epitopes to patients with lung cancer.
Combinational approaches to cancer treatment
Over 50% of head and neck cancer cases contain cancer associated myofibroblast (CAFs) which impede the ability of cytotoxic T cells to attack cancer. Nox4 enzyme is critical for promoting and maintaining the myoCAF phenotype. Together with Prof Gareth Thomas’s group at the University of Southampton, we recently showed that inhibition of this enzyme in fibrotic cancers helps cytotoxic T cells induced by vaccines migrate into cancer to mediate anti-cancer attack. One of the approaches which is being explored is targeting of myoCAFs with vaccines, once antigens expressed by myoCAFs have been fully characterised. We also continue to explore, further, how approaches to combine vaccination with CAF targeting can be harnessed to improve treatments for head and neck cancer and other fibrotic cancers.