Dr. Jason Luke on Potential for IDO Inhibitors in Melanoma

Jason Luke, MD
Published: Wednesday, Oct 12, 2016


Jason Luke, MD, Assistant Professor of Medicine, The University of Chicago Medicine, discusses IDO inhibitors in melanoma.
 
Some patients have an immune infiltrate in their tumor and when that is present the T-cells drive an inflammatory phenotype in which the tumors cells react to the immune cells that are in the tumor microenvironment, upregulating certain molecules, including PD-L1, says Luke.
 
However, there are a number of other molecules that are activated in parallel with PD-L1, including IDO. That molecule is a suppressive enzyme that catabolizes tryptophan into kynurenine. This causes the tumor to upregulate the molecule to block the immune cells that have come into the tumor microenvironment to kill the cancer, and by blocking both of the mechanisms at once, IDO and PD-1 or PD-L1, there is a dramatic increase in the efficacy of the treatment, says Luke.
 
The IDO molecule does not have enormous impact on normal physiology, so by blocking it there is no additional toxicity. The combination of IDO and PD-1 antibodies so far have had no increase in toxicity relative the PD-1 antibody alone, says Luke.
 

Jason Luke, MD, Assistant Professor of Medicine, The University of Chicago Medicine, discusses IDO inhibitors in melanoma.
 
Some patients have an immune infiltrate in their tumor and when that is present the T-cells drive an inflammatory phenotype in which the tumors cells react to the immune cells that are in the tumor microenvironment, upregulating certain molecules, including PD-L1, says Luke.
 
However, there are a number of other molecules that are activated in parallel with PD-L1, including IDO. That molecule is a suppressive enzyme that catabolizes tryptophan into kynurenine. This causes the tumor to upregulate the molecule to block the immune cells that have come into the tumor microenvironment to kill the cancer, and by blocking both of the mechanisms at once, IDO and PD-1 or PD-L1, there is a dramatic increase in the efficacy of the treatment, says Luke.
 
The IDO molecule does not have enormous impact on normal physiology, so by blocking it there is no additional toxicity. The combination of IDO and PD-1 antibodies so far have had no increase in toxicity relative the PD-1 antibody alone, says Luke.
 



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