Homing in on cancer targets

Published: 20-May-2015

Traditional cancer treatments like chemo- and radiotherapy are blunt instruments. Dr Sarah Houlton looks at developments in CAR T-cell technology, which promises a much more precise approach

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The interest in personalised treatments in the cancer arena continues to grow apace, as evidenced by the recent focus on CAR T-cell therapies. Immunotherapies like CAR T have huge potential advantages over the traditional blunderbuss-style chemotherapy and radiotherapy treatments that have dominated cancer regimens for decades, and even the more targeted kinase-based therapies that have been reaching the market in recent years. They are designed to use the patient’s own immune system to fight off the cancer.

CAR T-cells, or chimeric antigen receptor T-cells, are T-cells that have been engineered to have specific receptors that enable them to precisely target cancer cells. The T-cells are harvested and the receptor for their cancer is grafted onto the cells. The cells are then administered to the patient, ready to home in on the cancer cells, and multiply in the presence of the antigen to increase cancer-killing potential.

CAR T-cells can be constructed in a variety of ways using different protein domains

CAR T-cells can be constructed in a variety of ways using different protein domains. Most commonly, they have an extracellular domain designed to recognise the target antigen on the tumour cell, which is usually antibody-derived. This is linked to the cell’s transmembrane domain via a suitable spacer, and is in turn attached to an intracellular domain. This activates the cell when that target antigen has been recognised. The intracellular domain also often incorporates further co-stimulatory proteins to improve the response and durability of the T-cells. In this way, the CAR T-cells are engineered to seek out and destroy tumour cells.

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