Investigating IgG cell depletion mechanisms

About the project

The University of Southampton invites you to apply for a PhD studentship sponsored by UCB BioPharma UK.

Antibody-based therapies have had great success in treating cancer indications via targeted depletion of pathological cells. Antibody-dependent depletion utilises a spectrum of mechanisms to kill cells including antibody-dependant cellular cytotoxicity (ADCC), complement dependent cytotoxicity (CDC), antibody dependent cellular phagocytosis (ADCP) and direct cell death (DCD). It is however unclear if clinical success is governed by any specific dominant mechanism in vivo.

Therefore, for the best possible clinical outcome, a sensible approach is to develop antibodies that have broad spectrum depletion properties. Limitations to successful depletion include the nature of the target (size, membrane proximity, internalisation, target density) and properties of the antibody (epitope, affinity, and antibody format). Efforts to enhance depletion, such as by reducing fucosylation to increase ADCC and enhancing hexamerisation to augment CDC, have emerged as beneficial strategies to improve a specific depletion MOA. Another unanswered question is whether mAb combinations can elicit more powerful depletion effects.

This PhD will systemically explore the relationship between specific properties of the antibody (for example: affinity, valency, isotype, glycosylation, Fc mutations), the nature of the target (for example: size, target density and epitope) and depletion mechanisms. It will investigate mAb combinations and employ model target systems in combination with well-established antibody Fc variants to probe and differentiate between ADCC, CDC ADCP and DCD whilst also exploring unique UCB technologies designed to augment certain effector mechanisms.

The PhD will be supervised by Professor Mark Cragg and based at the University with industrial supervisory support provided by Dr. Emma Davé and Dr. Shirley Peters at UCB in Slough, UK.

About UCB

UCB Pharma is a global biopharmaceutical company, with a focus on neurology and immunology. UCB Biopharma UK has an excellent infrastructure and is well-equipped with state-of-the-art technologies including antibody discovery platforms capable of discovering antibodies with broad epitope diversity, and tools and methodologies to produce modified antibodies and antibody formats.

The company also offers hands-on training in multidisciplinary and intersectoral research. UCB Pharma are highly experienced in the training of PhD students and promote equal gender opportunities.

Professor Mark Cragg

• Antibody biology
• Antibody engineering
• Cancer Immunotherapy

Professor Ali Roghanian PhD, FHEA

• Cancer immunotherapy
• Monoclonal antibodies
• Cellular therapies (e.g., CAR T and iNKT cells)

Entry requirements

A UK 2:1 honours degree and/or a second degree with a related master's in one of the following fields:

• molecular biology
• immunology
• cell biology

Fees and funding

For UK students, £4596 tuition fees and a stipend of £17,668 tax-free each year for up to 4 years.

This studentship is funded by UCB.

How to apply

Apply now

You'll need to add Mark Cragg as your proposed supervisor.

Applications should include:

• your cv (resumé) including contact details of 2 referees
• academic transcripts to date
• a personal statement outlining your suitability for the studentship, what you hope to achieve from the PhD, and your research experience to date

Faculty of engineering and physical sciences

Email: fmed-gradschool@soton.ac.uk

Project leader

If you wish to discuss any details of the project informally, please contact Professor Mark Cragg.

Email: msc@soton.ac.uk

Research areas