Big opportunities for small molecules in immuno-oncology

JL Adams, J Smothers, R Srinivasan… - Nature reviews Drug …, 2015 - nature.com
JL Adams, J Smothers, R Srinivasan, A Hoos
Nature reviews Drug discovery, 2015nature.com
The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer
immunotherapies with durable clinical effects. Most of these breakthrough medicines are
monoclonal antibodies that block protein–protein interactions between T cell checkpoint
receptors and their cognate ligands. In addition, genetically engineered autologous T cell
therapies have also recently demonstrated significant clinical responses in haematological
cancers. Conspicuously missing from this class of therapies are traditional small-molecule …
Abstract
The regulatory approval of ipilimumab (Yervoy) in 2011 ushered in a new era of cancer immunotherapies with durable clinical effects. Most of these breakthrough medicines are monoclonal antibodies that block protein–protein interactions between T cell checkpoint receptors and their cognate ligands. In addition, genetically engineered autologous T cell therapies have also recently demonstrated significant clinical responses in haematological cancers. Conspicuously missing from this class of therapies are traditional small-molecule drugs, which have previously served as the backbone of targeted cancer therapies. Modulating the immune system through a small-molecule approach offers several unique advantages that are complementary to, and potentially synergistic with, biologic modalities. This Review highlights immuno-oncology pathways and mechanisms that can be best or solely targeted by small-molecule medicines. Agents aimed at these mechanisms — modulation of the immune response, trafficking to the tumour microenvironment and cellular infiltration — are poised to significantly extend the scope of immuno-oncology applications and enhance the opportunities for combination with tumour-targeted agents and biologic immunotherapies.
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