Project: Macrocycle-mediated in vivo 'gluing' of T cells and cancer cells to improve T cell killing

2019-01-01 – 2022-12-31

Abstract

T lymphocytes play a critical role in tumor immunity by recognizing and subsequent killing of cancer
cells. Cold tumors that have limited or no T cell infiltrate, can be treated through infusion of ex vivo
engineered T cells. However, in the tumor microenvironment, T cells face a series of physical and
immune-biological barriers. Hence, we hypothesize that a window of opportunity exists for
strategies that enhance the affinity between a T cell and its target cancer cell. In this project, we will
investigate whether a synthetic approach for in vivo linking cancer cells and T cells allows for a more
efficient T cell based immunotherapy. Hereto we will develop a strategy for engineering the T cell
surface with synthetic ligands for efficient cancer cell binding, and a strategy for engineering the
cancer cell surface to be easily recognized by T cells. Key in our approach is the use of cyclic
polymers (i.e. macrocycles), that are known to have superior resistance to aspecific adsorption and
we hypothesize that macrocycles exhibit restricted coiling, which should lead to improved receptor
affinity of ligands substituted onto a macrocycle backbone.