Modelling Tumour Immunotherapy: Investigating T-cell engaging therapies in Oncology

In immunotherapy, cancer is treated by using the body's immune system, enabling it to recognize and kill cancer cells. There are several approaches to harness the tumour-killing capacity of the T cells and an emerging class of therapeutics in Oncology is the use of T-cell engagers (TCE). T-cell Engagers (TCEs) are biological molecules that are at least bi-specific: they bind both a target tumour antigen (TAA) and a receptor on a T-cell, such as CD3, with the intention of activating the T-cell to destroy the tumour cell. The concept has been demonstrated pre-clinically and clinically, and drugs with such a mechanism of action have been approved for patients.
Appropriate dosage of a molecule requires an understanding of a surrogate of instantaneous target engagement in a patient. However, their development remains largely empirical while the precise relationship between the drug characteristics, its effect and accompanying potentially serious adverse events remain poorly defined.

In this project, we aim to develop data-driven mathematical and computational models (ODEs, PDEs and agent-based approaches) to investigate the role of T-cell engagers in targeting tumour cells. We aim to study the mechanism of trimer formation and investigate features that determine the TCE efficiency to inform the development and optimisation of TCE based therapy.