The T cell druggable genome

3 September 2012  •  Author(s): Jan Diekmann, Martin Löwer, John C. Castle, Sebastian Kreiter, Özlem Türeci and Ugur Sahin, Translational Oncology, Johannes Gutenberg Medical University of Mainz

The ‘druggable genome’ has been defined as those genes that can be pharmaceutically modulated; when intersected with disease-associated genes, the resultant set represents therapeutic targets for developing drugs to prevent and treat diseases. Historically, druggable therapeutic target genes have been defined by two features; (i) their significant contribution to the disease phenotype in a sufficient number of affected individuals and (ii) modulation of their activity by binding of a drug molecule.

The emerging era of cancer immunotherapy is dramatically changing the target landscape towards molecules that can be recognised by antibodies and T cells, thereby inducing redirection of immune effector mechanisms against target-bearing tumour cells. Despite the fact that the target space for immunotherapy is broad, few genes have been clinically evaluated as cancer immunotherapy targets. We have recently shown that patient and tumourspecific somatic mutations identified by next-generation sequencing of cancer genomes can be systematically targeted by cancer vaccines. In combination with a versatile immunotherapy platform for on-demand production of tailored vaccines, this, for the first time, opens the door to an entirely new source of druggable therapeutic targets – the abundant space of individual cancer mutations.

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