Anti-cancer immune responses following bispecific T cell engager therapy

About the Project

Background: Treatment of blood cancers has undergone an immunotherapy revolution. Numerous therapies now exist which expose cancer cells to the immune system and trigger anti-cancer T cell responses. Bispecific T cell engagers (BITEs) are a class of immunotherapies at the forefront of this revolution. They are antibody-based drugs with two ‘arms’- one which binds T cells and one which binds a cancer cell target. This leads to T cell activation and cancer cell killing. While there are clear benefits of these therapies, much still needs to be learned about why some patients don’t respond and how we can encourage maximum responses to these treatments.

This project: Recent work from our group suggests that cancer cell killing may occur in two phases- an immediate phase during BITE therapy, and a memory phase that persists after BITE therapy. This PhD will test the hypothesis that BITE therapy provokes sustained antigen-specific T cell responses.You will study samples from a prospective cohort of patients undergoing BITE therapy for lymphoid cancer, performing antigen- induced marker assays and characterizing T cells using flow cytometry, single cell RNA sequencing and T cell receptor repertoire analysis. The project will involve both wet lab and bioinformatic work (approximately 50:50). You will be supervised and trained by dynamic and supportive research teams with expertise in both.

Importance/ Impact: Given the rapid expansion of BITE therapies, answering this fundamental question is timelyand has the potential to impact treatment protocols and patient outcomes. BITEs will be increasingly used to spare patients from toxicities associated with conventional chemotherapy. Optimising responses to BITEs could therefore prevent some of the lifelong health complications experienced by chemotherapy-treated children and permit curative treatment to be offered to older, less fit adults.

Funding

Students who have, or are expecting to attain, at least an upper second-class honours degree (or equivalent) in a relevant subject, are invited to apply. Funding is available for Home (UK) students to cover tuition fees, a tax-free stipend at the UKRI rate (indicative amount in year 1 in 2026-27, £21,805) and research costs, for four years. Applicants normally required to cover International fees will have to cover the difference between the Home and the International tuition fee rates. There is no additional funding available to cover NHS Immigration Health Surcharge (IHS) costs, visa costs, flights etc.

Funding for this studentship is awarded on a competitive basis and is not guaranteed; availability will depend on the outcome of the selection process and subject to final approval by the University.