James P. Allison

I mean, it's not that it always happens. I know of at least one marathoner who got melanoma and went through the whole course of therapy and never missed a race. Oh, wow. Okay. Other people get very sick. And sometimes there can be things which can be fatal. Thank God they're rare.

I mean, it's not that it always happens. I know of at least one marathoner who got melanoma and went through the whole course of therapy and never missed a race. Oh, wow. Okay. Other people get very sick. And sometimes there can be things which can be fatal. Thank God they're rare.

And the clinicians now know from experience, just developed algorithms for recognizing when it's about to happen and heading it off or at least reversing it early on while you've still got time.

And the clinicians now know from experience, just developed algorithms for recognizing when it's about to happen and heading it off or at least reversing it early on while you've still got time.

Drugs in the form of, right now, one of the popular things are antibodies. These are just proteins that we can make that are very specific. I mean, that's what we did with CTLA-4 in the 90s. There was this molecule, and it was funny. It looked like a molecule that was the gas pedal of T cells, but this molecule called CTLA-4, and we showed that it was actually not a gas pedal, it was a brake.

Drugs in the form of, right now, one of the popular things are antibodies. These are just proteins that we can make that are very specific. I mean, that's what we did with CTLA-4 in the 90s. There was this molecule, and it was funny. It looked like a molecule that was the gas pedal of T cells, but this molecule called CTLA-4, and we showed that it was actually not a gas pedal, it was a brake.

And the people that called it a gas pedal, what they did was they had T cells that put them in culture, activate them, and then add an antibody, and they'd get more. And they said, okay, well, that's a gas pedal. That's what we did earlier in the 80s, showed that CD28s and other molecules, like the gas pedal. So the antigen receptor you could think of is the ignition switch. That's all it is.

And the people that called it a gas pedal, what they did was they had T cells that put them in culture, activate them, and then add an antibody, and they'd get more. And they said, okay, well, that's a gas pedal. That's what we did earlier in the 80s, showed that CD28s and other molecules, like the gas pedal. So the antigen receptor you could think of is the ignition switch. That's all it is.

It tells a T cell. But a T cell has to get a second signal. at the same time, which is like the gas pedal, and that's a molecule called CD20A that we showed in the late 80s, was the gas pedal. If you don't push on that, activating through the antigen receptor doesn't do you any good at all. The T cells don't do anything.

It tells a T cell. But a T cell has to get a second signal. at the same time, which is like the gas pedal, and that's a molecule called CD20A that we showed in the late 80s, was the gas pedal. If you don't push on that, activating through the antigen receptor doesn't do you any good at all. The T cells don't do anything.

Tumors never have, solid tumors, I should say, don't have the structure that binds to that gas pedal. So it's complicated. So tumors are inherently, solid tumors are invisible to the immune system because they don't have that second signal. The only way they get them is to the tumor. And we worked this out in the early 90s. The tumor gets big enough or whatever causes inflammation.

Tumors never have, solid tumors, I should say, don't have the structure that binds to that gas pedal. So it's complicated. So tumors are inherently, solid tumors are invisible to the immune system because they don't have that second signal. The only way they get them is to the tumor. And we worked this out in the early 90s. The tumor gets big enough or whatever causes inflammation.

The innate immune system comes in. The innate immune system has those things that they're called B7 for B7.

The innate immune system comes in. The innate immune system has those things that they're called B7 for B7.

they can be called frank it doesn't matter i mean it's just the name means nothing but they buy the cd28 and that's that says go so the only way that the immune system with solid tumors and this is that we published this there in the early 90s was uh when you that they grow until there's tumor cell death and the innate immune system comes in and primes the T cells.

they can be called frank it doesn't matter i mean it's just the name means nothing but they buy the cd28 and that's that says go so the only way that the immune system with solid tumors and this is that we published this there in the early 90s was uh when you that they grow until there's tumor cell death and the innate immune system comes in and primes the T cells.

And then you start generating T cells. But the thing is you probably got 10 to the 10th, 10 to the ninth different, nobody really knows for sure, but different T cells in your body with different receptors. And of course that means you've only got a few hundred maybe of any given clone. And that's not enough to protect you against anything. You need hundreds of thousands.

And then you start generating T cells. But the thing is you probably got 10 to the 10th, 10 to the ninth different, nobody really knows for sure, but different T cells in your body with different receptors. And of course that means you've only got a few hundred maybe of any given clone. And that's not enough to protect you against anything. You need hundreds of thousands.

And so they have to expand. And so that's what this, so the T cell receptor sees the ignition switch. And then when you, but nothing happens really until you push on the CD28 molecule, the gas pedal, then they take off. You got to generate a hundred thousand. I mean, you've got hundreds of thousands to millions of cells to swarm through the body and look for things.

And so they have to expand. And so that's what this, so the T cell receptor sees the ignition switch. And then when you, but nothing happens really until you push on the CD28 molecule, the gas pedal, then they take off. You got to generate a hundred thousand. I mean, you've got hundreds of thousands to millions of cells to swarm through the body and look for things.