Cancer Immunology and Computational Biology PhD: Developing novel antibody-based immunotherapies for the treatment of Glioblastoma

Application Deadline:      Jan 6^th 2025

Project Start Date:            May 1st 2025

About the Project

Antibody immunotherapy has significantly improved survival rates for both haematological and non-haematological malignancies. These antibodies function by either directly targeting tumour cells for destruction (e.g., rituximab) or by activating critical immune cells within the microenvironment to elicit a potent immune response (e.g., pembrolizumab). However, the range of antigens targeted by clinically approved antibodies is limited, and research suggests that expanding these capabilities could further enhance immune system reactivation within the tumour microenvironment.

Glioblastoma (GBM) is a lethal and highly therapy-resistant primary brain tumour with no adequate therapies, underscoring the urgent need for improved patient outcomes. Antibody immunotherapy has been relatively underexplored in this context due to the misconception that antibodies cannot penetrate the blood-brain barrier (BBB). However, research from our lab has shown that in orthotopic models of murine GBM, systemically administered antibodies can cross the BBB and modulate the immune system by depleting T regulatory cells (Tregs), thereby improving survival outcomes. This project aims to investigate whether this modulation can be further enhanced in vivo using bi-specific antibodies to also target the innate immune system and to assess the translatability to humans using patient-derived explant models.

The aim of this project is to generate bi-specific antibodies that engage the innate immune system and synergise with Treg depleting agents to enhance immunotherapy for the treatment of GBM:

1)   Engineer novel bi-specific antibodies from in silico to protein purification and test in vitro, in vivo and ex vivo to ascertain the most effective way to activate the innate immune system

2)   Utilise the orthotopic NPE glioblastoma murine model to investigate the efficacy of monotherapy and combination therapy using the developed bi-specific antibodies

3)   Using bioinformatic methods, access the intrinsic & extrinsic pathways, as well as the interactions between the innate and adaptive immune system in both murine and human models of GBM

Supervision and Support:

You will have a primary and subsidiary supervisor (tbc). The Primary Supervisor is Prof Sergio Quezada (UCL Cancer Institute) [Email Address Removed].You are welcome to contact the supervisor for informal enquiries and questions.

Formal supervisory meetings will be once weekly with primary and/or secondary supervisors. Students are also supported by a Thesis Committee.

The student will participate in the UCL CI CIRPS seminars, departmental seminars and weekly lab meetings in addition to the UCL teaching and training meetings.

All students take part in a compulsory first year Cancer programme and are part of the UCL Doctoral School’s Development Training Programme. All students complete 20 training points per year as part of their researcher development.

About the Department

The PhD student will be based at the UCL Cancer Institute joining Prof. Quezada and his team at UCL Cancer Institute embedded within the CRUK City of London Centre (https://www.colcc.ac.uk).

The University College London Cancer Institute (UCL CI) is the hub for cancer research at UCL, one of the World's leading universities. The Institute draws together over 400 talented scientists and over 150 PhD students who are working together to translate research discoveries into developing kinder, more effective therapies for cancer patients.

The Quezada Lab (Immune Regulation and Tumour Immunotherapy Group) is dedicated to unravelling the intricate mechanisms that govern immune recognition of cancer and the regulation of anti-tumour immunity. Our research focuses on understanding the complex interactions within the tumour microenvironment and the fundamental principles that drive immune responses against malignancies. By leveraging these insights, our goal is to identify and develop novel therapeutic targets, ultimately advancing the next generation of immunotherapies to improve outcomes for cancer patients.

Entry Requirements

A UK master’s degree, or a minimum of a first or a high upper second-class UK Bachelor’s degree, in a relevant discipline, or an overseas qualification of an equivalent standard. Candidates will need to demonstrate a strong research component.

Essential experience: in molecular biology techniques including vector manufacturing, antibody engineering, protein purification, data analysis and computational biology are essential.

Experience in cell culture and basic wet lab techniques as well as in vivo mouse models of cancer immunology, and high dimensional flow cytometry are also essential to this role. We welcome applicants from disadvantaged backgrounds, or via an unconventional career path.

English Language Requirements

If your education has not been conducted in the English language, you will be expected to demonstrate evidence of a good level of English proficiency. The English language level minimum for this programme is: level 3.

Deadline and Application Process

The deadline for submission is: Jan 6^th 2025

Interviews will be online in the latter part of January. Successful candidates will be invited to visit the laboratory and meet members of the team.

To apply please send your selection materials to [Email Address Removed]:

1.   A CV

2.   Two academic/ professional references: two scientists/ academics who are familiar with your academic work and/ or research experience and who can judge your potential as a PhD student. One should be your current or most recent employer/supervisor, at least one must be able to comment on your university academic record, and at least one must be able to comment on your previous research experience.

3.   Transcript/s of the marks you achieved in your qualifications.

4.   In your 1 page statement, please expand on:

a.   why you want to do a PhD and why this one,

b.   what are your career aspirations and previous experience.

c.    Please give details on your research experience in cell culture and wet lab techniques, molecular biology, data analysis and computational biology as part of your statement.

Shortlisting will be immediately after the closing date so please make sure all your documents and your referees have provided their references before so your application can be processed. Shortlisted candidates only will be asked to apply formally through UCL.

We wish you every success in your application.