Development of a novel PCR-based assay to evaluate CAR-T safety using a human-based genotoxicity model

The project on offer is to develop a model for the evaluation of safety when using immunotherapy. CAR-T therapy is currently a novel approach to treat cancer using T cells infected by lentivirus vector carrying CD-19 gene cassettes.

The viruses insert themselves, upon infection, into the host genome in order to express the CAR gene cassette. This boosts the T cells that are now called CAR-T cells to kill tumours once returned to the host.

Our work is to generate T cells from induced pluripotent stem cells and test whether virus infection activates cancer genes. We have IP on this technology and expect further IP to be generated. We also have a spin-out company, which the student will be working with and representing during the study. In the future, we hope positions will become available in the company – TestAVec Ltd.

Supervisor's interests

Our research concerns the safety of using gene therapy for rare diseases and cancer. We have previously received funding from the NC3Rs to develop alternatives to animals for this work. I have previously successfully supervised over 20 PhD students with many going on to careers in this space.

My work involves developing models of gene therapy safety for retroviruses, lentiviruses, adenoviruses and adeno-associated viruses. We generate these viruses in-house and offer strong supervision in the techniques used to study these vectors. We also work with induced pluripotent stem cells as an alternative to mouse studies. Our group collaborates worldwide and we offer places to present our competitive research at national and international conferences.

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

1. Contact the supervisor by email or phone to discuss your interest and find out if you would be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

Good luck!

This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

Meet the Supervisor(s)

Michael Themis - Dr Themis is a Reader in the Department of Life Sciences Brunel University London and an Honorary Lecturer at Imperial College, London. His research at Brunel concerns gene therapy efficacy and safety. Founding Director of TestaVec Ltd - A brunel University spin-out company Between 2015 and 2017 over 1800 gene therapy (GT) trials were initiated or approved worldwide. Large pharmaceutical companies including GSK, Novartis, Astra Zeneca and Pfizer are investing heavily in gene therapy virus technology and two new licensed products, ‘Glybera” (Uniqure) and Strimvelis (GSK) have now entered the market. Treatments for several genetic disorders are available including cancer, however, no standardised platform has been available to test safety, which is concerning following the development of leukaemia in several children treated for X-linked immunodeficiency by this therapy. Dr Themis has recently launched the first company that focusses on screening the safety of gene therapy. The technology developed and led by Dr Themis in collaboration with UCL, KCL, GeneWerk, Germany, the National Institute for Biological Standards and Control and NMI, Germany, won the SBRI InMutaGene CRACK-IT Challenge. This work, which was funded by the NC3Rs and sponsored by GSK and Novartis has generated the first human induced pluripotent stem cell (iPSc) based platform that evaluates the safety of gene therapy products. The intension is to use this technology prior to patient exposure as a pre-screening service that identifies patient tolerance to gene therapy and to profile vector side effects next to established reference standards. With IP filed, TestaVec Ltd, which is a spin-out of Brunel University will support academics and industry alike to enter their products safety into the clinic. Qualifications: -

• BSc: 1st class honours with Brunel University London and University Prize
• PhD: 1994 entitled “Insertional mutagenesis:experiences at the hprt locus”
• Post Graduate Certificate in Learning and Teaching in Higher Education (PGCert)
• Post Graduate Certificate in Intellectual Property Law (PGCert)

Training - Persuasion and Assertiveness - 2008 PgCert in Teaching - 2008 PgCert in Patent Law - 2010 Blackboard Learn - 2012 Biological Monitoring for Health and safety – HSE Buxton 2012 Introduction to the Principles and Practices of working at Containment Level 3 – HPA Porton Down 2013