Chicago, Jim Allison, Carl June discussed on The Long Run

The Long Run


Body that's designed to balance to be balanced. We have to recognize everything that's foreign, whether it's a virus or a bacteria or if you put a kidney from one person into somebody else that all has to be balancing act because you don't want the infection to take hold. So the immune system builds a set of to go after things that are foreign. Unfortunately, it makes mistakes and the mistakes are that it's thinking sometimes that it sees something foreign. And it starts attacking self. And that's what autoimmune diseases are. It destroys a kidney transplant when you don't want it to. And so that balancing act always intrigued me and that was what I was studying at the NIH when I was there in the national cancer institute was immune tolerance. How to enable it And so when I got to Chicago, we started for the first time understanding what were the molecular basis of this discrimination between self and non self. And that led to a discovery of really some of the most important pathways that we now utilize in all fields. We learned that in order for an immune cell specifically a T cell to get activated, it needed to recognize what was foreign and get a booster signal called the co stimulatory signal. But in the process, that often broke tolerance and you started recognizing things you didn't want to recognize. So one of the first, I would say important discoveries I made while in Chicago was developing a drug that's actually now on the market to treat a number of autoimmune diseases called abatacept and Belarus and these drugs block that co stimulatory signal. So T cells instead of getting turned on when they shouldn't be get turned off. And so that idea of turning on and turning off on the one hand, we were talking about stopping the gas from getting turned on. And then that led me to the discovery of CTLA four as a break that turned off the immune system when you didn't want it to work. And so those Chicago days were so much fun because everything we learned was unexpected in serendipitous. Every time I think I knew what to expect, we got the opposite result. And it was great early days with Jim Allison and Craig Thompson and Carl June and all the people that really were studying these co stimulatory pathways and checkpoint pathways. And it was, it was pretty exciting, but it gets back to this idea that once we started understanding the rules, once we start to understanding that the immune system was this on off yin Yang, then we could start shifting it, where we wanted to get more breaking of tolerance for cancer. We knew how to do that. When we wanted to start introducing things that would shut down the immune response and type one diabetes we could do that. And it was a really exciting time for really understanding what the rules were about how the immune system does this self non self discrimination. So there's all this basic science going on figuring out the rules as you say for how the immune system works. But it took a long time to be applied. In the field of cancer, it really is well known CTLA four you mentioned is the target of the drug now marketed by breast and Myers. Your boy. It's one of those checkpoint inhibitors that this breaking mechanism that tumors actually use to shield themselves from that T cell attack. And if you can sort of sable that, the immune system can now attack the tumors. This is like foundational. This is a huge, it's the birth of a whole new industry. What was it like to see that really come to fruition years later? Yeah. Right. I think you're emphasizing it with both exciting and frustrating, right? Because that discovery we made was in 1994. It wasn't until the late 2000s, 2011, something like that that your boy got approved. So it took a long time from that basic science to discovery to the drug. And a lot of perseverance perseverance by a lot of people. So in that sense it was frustrating. But it was also exciting because it was really changing. It was changing a field and changing the way we think about cancer treatments. And in that sense, it was exciting if nothing else to be the fly on the wall. But as I said, this frustration always stuck with me, which is why one day I decided if I'm going to see something that I've been involved in creating making all the way, maybe I've got to get involved in it myself. So all this cancer work is happening. You mentioned some of the people who are well known for their role in this. But you're a lot of your work as you mentioned was in diabetes and the other side of the coin. And could you say a little bit about founding this immune tolerance network? Why did you do that? Why was that important? Yeah, so this was a great opportunity, a unique opportunity that I had. Again, we're at the border of University of Chicago and UCSF in 1999. And I was approached by basically Tony Fauci at the time a name now that everybody knows about his idea to create this network to be able to study immune tolerance because he, in the early days of what we would now call precision medicine. He really felt that if we could understand better how to treat the immune system for autoimmunity, that would impact our ability to treat the immune system for asthma.

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