Faculty: Science and Engineering
Supervisors: Dr Saqlain Suleman ([email protected]); Prof Michael Themis (external) ([email protected])
Location: Cambridge
Match-funded by: TestAVec
Apply online by 8 February 2026We strongly recommend contacting the supervisors for this project for a discussion prior to applying.
Over 5,000 gene therapy trials have been listed with the National Institutes of Health (NIH). Most are viral vectors (80%) that include retrovirus (RV) and lentivirus (LV) due to their ubiquitous gene transfer capabilities, integration and long term and persistent therapeutic gene expression.
To meet safety requirements, several modifications have been made and RV have been replaced by HIV-1 based LV that can infect both dividing and non-dividing cells. These are mainly produced by human embryonic kidney cells (HEK 293T) by transient transfection with multiple plasmids or by inducible or non-inducible cell lines.
Chimeric antigen receptor (CAR) T cells have been used successfully in the targeting and treatment of several cancers, including leukaemia. This cell therapy involves using host T cells and transducing these with a HIV-1 LV to express a CAR epitope on the surface of T cells. These immune cells can then bind to specific targets only present on cancer cells to kill these cells.
International regulators including the British (MHRA), European (EMA) and American (FDA) regulatory agencies have raised concerns regarding the genotoxicity of these vectors. While these LV vectors are powerful tools for the treatment of diseases, side effects persist whereby the vector contributes towards insertional mutagenesis, dysregulation of the human genome and oncogenesi. This has been seen in CAR T therapy with secondary leukaemia, leading to the FDA issuing a black box warning to be present on all CAR T products, highlighting the risk of secondary cancer.
To address this, multiple models have been developed to understand the risk of mutagenesis. Dr Suleman and Prof Themis have developed the first and currently only human cell based model to understand the genotoxic risk of vectors to the human genome, commercialised through TestAVec.
This project aims to take induced pluripotent stem cells and differentiate these to T cell and generate CAR T cells after LV infection. The efficacy of these cells against tumour killing will be assessed and, using TestAVec’s patented model anmed the human individualised genotoxicity test (hingetox), you will understand the cancer related risk of these vectors with an aim to reduce the risk of cancer due to CAR T cell therapy. This will use a variety of molecular biology endpoints including insertion site identification, clonal tracking, transcriptomic and epigenetic analyses.
This project will primarily be based at ARU's Cambridge campus, with travel involved to the TestAVe facilities in London. It is expected that the successful candidate will be able to travel between both labs.
Apply online by 8 February 2026The successful applicant for this project will receive a Vice Chancellor’s PhD Scholarship which covers the tuition fees and provides a UKRI equivalent minimum annual stipend for 3.5 years. For 2025/6 this was £20,780 per year. The award is subject to the successful candidate meeting the scholarship terms and conditions. Please note that the University asserts the right to claim any intellectual property generated by research it funds.