Very interesting information for all of us. Checkpoint inhibitors modulate an immune response. So if there is no immune response, they will not function. Sometimes people forget that.
It would be interesting to speculate that the minority of recurrent GBM patients that have responded to PD-1 inhibition alone in the preliminary trials might have been hypermutated, which studies in other cancers show is predictive for response to these PD-1 antibodies.
Hypermutation = more neoantigens for the immune system to recognize as non-self
http://www.nejm.org/doi/full/10.1056/NEJMoa1500596#t=article "PD-1 Blockade in Tumors with Mismatch-Repair Deficiency"
"An existing drug known as a JAK inhibitor may help patients who don't respond to the so-called checkpoint inhibitor immunotherapy drugs overcome that resistance, suggests a new preclinical study. Importantly, the results demonstrate that shutting down the interferon pathway, shown here to be critical to a tumor's resistance to immunotherapy, with a JAK inhibitor may improve checkpoint inhibitor drugs and even bypass the need for combinations of these drugs, which often come with serious side effects."
Interesting, though insurance companies are very unlikely to approve ruxolitinib for GBM, and cost in the US for a 28 day course is about $7000-$9000.
On the other hand, consider propranolol, a cheap off-patent drug that could cost as little as $15 per month. Improves response to tumor lysate vaccines in mouse models.
Very interesting information for all of us. Checkpoint inhibitors modulate an immune response. So if there is no immune response, they will not function. Sometimes people forget that.
ReplyDeleteIt would be interesting to speculate that the minority of recurrent GBM patients that have responded to PD-1 inhibition alone in the preliminary trials might have been hypermutated, which studies in other cancers show is predictive for response to these PD-1 antibodies.
DeleteHypermutation = more neoantigens for the immune system to recognize as non-self
http://www.nejm.org/doi/full/10.1056/NEJMoa1500596#t=article
"PD-1 Blockade in Tumors with Mismatch-Repair Deficiency"
Very interesting, thank you for sharing.
ReplyDeletehttps://www.sciencedaily.com/releases/2016/12/161201164457.htm
ReplyDelete"An existing drug known as a JAK inhibitor may help patients who don't respond to the so-called checkpoint inhibitor immunotherapy drugs overcome that resistance, suggests a new preclinical study. Importantly, the results demonstrate that shutting down the interferon pathway, shown here to be critical to a tumor's resistance to immunotherapy, with a JAK inhibitor may improve checkpoint inhibitor drugs and even bypass the need for combinations of these drugs, which often come with serious side effects."
Interesting, though insurance companies are very unlikely to approve ruxolitinib for GBM, and cost in the US for a 28 day course is about $7000-$9000.
ReplyDeleteOn the other hand, consider propranolol, a cheap off-patent drug that could cost as little as $15 per month. Improves response to tumor lysate vaccines in mouse models.
https://www.ncbi.nlm.nih.gov/pubmed/27899275