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Small Molecule Inhibitors as an Alternative to Antibody Blockade in Immunotherapy

Christopher E Rudd and Alison Taylor

The application of immune checkpoint blockade for the treatment of cancer has revolutionized immunotherapy regimes over the past few years. This approach has seen much success using antibody blockade of programmed cell death-1 (PD-1) or its ligand, PD-L1. However, there are many limitations to antibody blockade, including cost, tumour penetration and autoimmune complications. Patients may suffer from adverse side effects and many remain uncured. Combination of therapies with antibodies can improve response rates, but may also increase serious side effects. Here, we look at the use of small molecule inhibitors as an alternative to antibodies in targeting intracellular pathways for co-receptor blockade and synergies in immunotherapy.