Immunotherapy has been featured a lot on this blog because of the potential to dramatically improve the survival rates of cancer patients, including those struck by melanoma. Obviously, I’m not the only one excited about the progress made in this field. This year’s Nobel Prize in medicine was awarded to two immunology researchers – Dr. James Allison of the MD Anderson Cancer Center and Dr. Tasuku Honjo of Kyoto University.
Because of the work led by these two gentlemen, we understand quite a bit more about the functioning of T cells at a molecular level. I mentioned the work done by Dr. Allison on CTLA-4 in a previous post regarding the history of immunotherapy. I won’t rehash it here but you can read more if you’d like. Basically, CTLA-4 is a protein receptor that acts as a brake on the immune system (or if you love jargon, it downregulates immune responses). Dr. Honjo discovered PD-1 (also mentioned quite a bit recently in this blog). PD-1 is a protein on the immune system’s T cells. When it is bound with another protein called PD-L1, it also “downregulates immune responses”. Cancer cells have evolved to lock up both of these proteins, in essence, shutting down the body’s immune system from finding and destroying the cancer cells, giving the cancer cells the ability to spread unchecked. The research on both of these cell proteins came to the conclusion that if we could develop drugs to stop the expression of these proteins, we could allow the T cells to go on a seek-and-destroy mission against cancer cells.
Researchers built on the work pioneered by these two men and developed the first round of checkpoint inhibitor drugs ipilimumab (aka Yervoy), nivolumab (aka Opdivo) and pembrolizumab (aka Keytruda). It’s not hyperbole to say that these drugs have literally saved people’s lives. More recently, other checkpoint inhibitor drugs have been released that may have less severe side effects and more are in clinical trials.
Dr. Allison and Dr. Honjo discovered two totally separate proteins that do roughly the same thing to the immune system. For patients, that means that if one doesn’t work, there is still a chance the other will. Dr. Wolchok, a melanoma specialist, states in the article, ““These two pathways are very different. That’s good. They’re non-redundant. If patients don’t have the desired outcome from one we can use the other one. It speaks to the multiple different molecular brakes that exist to keep this powerful set of cells and organs that we call the immune system under control.”
Don’t get me wrong, immunotherapy isn’t the magic bullet that is going to erase cancer completely. But this line of research is opening new avenues for treating and even eradicating illness that would have once been hopeless outcomes. I am grateful to all of the men and women who worked with these two Nobel Laureates to get us to the point where we have a chance at controlling some forms of cancer as routinely as we control some other afflictions (bubonic plague, or heck, any other garden-variety bacterial infection before antibiotics were discovered) that were once considered death sentences.
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