Our research team at the University of Adelaide, led by Professor Shaun McColl, is developing a way to enable chemokine receptor mediated CAR-T active migration to solid tumours.
Chemokines are small cytokines, classified by their ability to induce chemotaxis (movement in response to a chemical stimulus) in nearby responsive cells. Some chemokines are ‘pro-inflammatory’ and can be induced during an immune response to recruit immune cells to an infection site; others are considered homeostatic and aid in controlling the migration of cells during normal bodily processes such as tissue maintenance or development. Chemokines affect the activity and behaviour of responsive cells by interacting with chemokine receptors on the surfaces of target cells. So far 19 different chemokine receptors have been characterised. Cells are ‘attracted’ by the chemoattractant of a chemokine concentration. Attracted cells move through the chemokine gradient towards the higher concentration of chemokines or source of chemokines.
Tumour cells and also cells in the tumour microenvironment produce chemokines. Each cancer has a specific chemokine profile and their production by the cancer results in a chemokine concentration gradient forming around the cancer. Our research program aims to enhance CAR-T tumour infiltration through the development of a dual-transduced CAR-T cell that expresses a chemokine receptor that can ‘home in’ to the chemokine gradient and more effectively direct the cancer-killing CAR-T cells to tumour cells.