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Antibody engineering to identify optimal expression systems and glycoforms of IgE class antibodies for cancer therapy


Project Description

Fully funded 4-year PhD Studentship with the MRC Doctoral Training Partnership at King’s College London

Applications Open: Friday 18th January

Application Deadline: Friday 1st March, 23:59

Supervisor Details

Co-supervisor 1A: Dr Sophia Karagiannis
Email:
Website: https://kclpure.kcl.ac.uk/portal/en/persons/sophia-karagiannis(3d3bd60b-872b-4547-b024-530ebfbec177)/biography.html

Co-supervisor 1B: Dr Gerd Wagner
Email:
Website: https://kclpure.kcl.ac.uk/portal/gerd.wagner.html

Partner Details: Ludger Ltd: https://www.ludger.com/

Project Description

Design strategies for cancer therapy have largely focused on one of nine human antibody classes, IgG1. We have designed an alternative approach by engineering anti-cancer antibodies bearing IgE Fc class regions. IgE antibodies are known to support immune defences against parasites and to be associated with allergies. These activities may be harnessed against cancer as a novel cancer immunotherapy strategy, exemplified by our first-in-class IgE antibody recognising a tumour-associated antigen undergoing a Phase I clinical trial at Guy’s Hospital.

IgEs are highly glycosylated antibodies, yet the precise effects of IgE glycan moieties on the potency and immune cell-activating mechanisms of IgE against cancer remain unclear. In this study, we aim to explore optimal engineering and glycoengineering strategies for the generation of anti-tumour IgE class antibodies in order to identify optimised antibodies for immuno-oncology. We will generate IgEs of the same specificity expressed in different mammalian expression systems and we will characterise their carbohydrate profiles in relation to function. Furthermore, we will generate different IgE glycoforms by administering inhibitors of glycan biosynthesis (Wagner). Antibody variant generation and pharmacological evaluations will be conducted in Year 1. Years 2-3 will focus on elucidating antibody biological functions, potency and ex vivo safety studies in patient blood and sera. Furthermore, glycoprofiling analyses (Ludger Ltd) will be conducted and correlated with antibody functional profiles. The study is designed to aid the identification of IgE antibodies and glycovariants with defined functional profiles and harbours considerable potential to deliver optimised antibody immunotherapies for clinical testing in oncology.

How to Apply

To apply to the MRC DTP iCASE Studentships visit our webpages to submit an online application via King’s Apply: https://apply.kcl.ac.uk/?aspxerrorpath=/%20%5bLink:%20https:/apply.kcl.ac.uk/

Further information can be found on our ‘Frequently asked Questions’ pages: https://kcl-mrcdtp.com/icase-studentships-faq/

Industrial Collaborative Awards in Science and Engineering (iCASE) Studentships: https://kcl-mrcdtp.com/icase-studentships/

This PhD project is fully-funded PhD 4 year position available to start in October 2019, with the successful candidate joining the MRC Doctoral Training Partnership: https://kcl-mrcdtp.com/

They will start immediately on their PhD project in October 2019 and will participate in all other training and cohort activities of the MRC DTP.

About Us

The objective of our Doctoral Training Partnership (DTP) is to select motivated and curiosity-driven students and provide them with outstanding training, tailored flexibly to their individual needs and interests: https://kcl-mrcdtp.com/

We will equip them with the intellectual and technical skills that are needed for undertaking cutting-edge biomedical research and complement this with key transferable skills (including public engagement, business development and entrepreneurship) to ensure that they emerge as well-rounded scientists, prepared for their next career stage (whether in research or outside). Our excellent clinical setting will ensure all students benefit from an understanding of the context of medical research, helping develop scientists with a strong translational ethos.

Eligibility

The MRC funding available supports Home/EU students within standard research council restrictions: http://www.legislation.gov.uk/uksi/2007/779/regulation/6/made

EU students are only eligible for a full studentship if they have lived, worked or studied within the UK for 3 years prior to the funding commencing: https://mrc.ukri.org/skills-careers/studentships/studentship-guidance/student-eligibility-requirements/

Unfortunately, we cannot accept applications from non-EU candidates.

If you have any questions, please get in touch with .

Applications Open: Friday 18th January

Application Deadline: Friday 1st March

Funding Notes

This studentship is fully funded for 4 years, including tuition fees, stipend, research consumables and conference travel:

Stipend: Students will receive a tax-free stipend for each year of study; for 2018/2019 this will be £19,277 per annum.

Bench fees: A generous allowance (£6,700) is provided for research consumables and for attending UK and international conferences. MRC DTP iCASE Students will also be eligible to apply for the Flexible Supplement Fund.

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