Genetic Engineering of Immune Effector Cells for CAR therapies using a Peptide Technology

Chimeric antigen receptor (CAR)-T therapies have demonstrated remarkable treatment outcomes and several CAR-T therapies now approved for treatment of haematological malignancies. However, the complex manufacturing process and use of the patient’s own cells increases costs, time to treatment and limits patient eligibility. NK cells are an attractive alternative for adoptive immunotherapy due to the unique ability for spontaneous cytotoxicity against cancer cells. CAR-NK cells present the advantage over CAR-T cells of unlimited use of allogenic NK sources without concern of graft-versus-host disease, and thus have the potential to be produced as an “off-the-shelf” product. Successful CAR immunotherapy depends on efficient and sustained transfer of the CAR transgene to immune cells. Safety concerns and expensive production with viral vectors warrants the development of novel non-viral delivery systems. Currently, electroporation and lipid nanoparticles are the main non-viral delivery methods for CAR transgenes, which have limitations due to poor cell viability and low transfection efficiencies. Peptides RALA and CHAT successfully deliver both DNA and mRNA to a range of immune cell lines in vitro without toxicity. This project will investigate the application of RALA and CHAT for sustained gene delivery, as a safer and more cost-efficient alternative to current CAR therapy manufacturing methods. 

Applicants should have a 1st or 2.1 honours degree (or equivalent) in a relevant subject. Relevant subjects include Pharmacy, Pharmaceutical Sciences, Biochemistry, Biological/Biomedical Sciences, Chemistry, Engineering, or a closely related discipline. Students who have a 2.2 honours degree and a Master’s degree may also be considered, but the School reserves the right to shortlist for interview only those applicants who have demonstrated high academic attainment to date. 

Postgraduate Research applicants must have applied to Queen’s, via the Direct Applications Portal. 

https://dap.qub.ac.uk/portal/user/u_login.php

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/PostgraduatePositions/ 

http://www.qub.ac.uk/schools/SchoolofPharmacy/Research/ 

 https://www.qub.ac.uk/schools/SchoolofPharmacy/Research/ResearchThemes/NanomedicineandBiotherapeutics/ 

https://pure.qub.ac.uk/en/persons/emma-dynes 

https://www.qub.ac.uk/schools/SchoolofPharmacy/Research/find-a-phd-supervisor/professor-helen-mccarthy.html 

Right from the start the PhD student will be involved in academic research designed to have translational/clinical application. This dual approach spans: 

1) Research Skills: the academic supervisors will ensure excellent training in nanoparticle formulation, systematic physical characterisation, in vitro cell and molecular biology techniques and potentially in vivo skills. 

2) Record keeping & monitoring: Monthly meetings with the student will take place with electronic records. Students must also complete a 3-month initial review and annual progress review to proceed to years 2 & 3. The annual progress review involves written work, presentation and/or mini viva. However, at each of these meetings, the primary supervisor will also be present ensuring that the maximal training benefit can be derived from these processes. 

3) Additionally, there will be opportunities to present at academic meetings, building professional networks, personal development on courses for animal licenses, advanced statistics, skills which are all relevant to subsequent employment opportunities. 

Impact activities include but are not restricted to presenting the research to academic and industry peers through scientific conferences and students from different disciplines through the Graduate School. The student will also engage with patients, clinicians and key stake holders through a series of webinars/focus groups to understand how they can feed and shape the research plan. Other impact activities relate to commercialisation though IP protection processes, competitor analysis and engagement with clinical collaborators.