James P. Allison

And so when you go with immunotherapy, and also there were some indications that maybe it was immunogenic, because there's a lot of mutations, but in any event, with our drug, 20% of people are cured by one or two injections of an antibody. The therapy, by the way, is you sit in a chair for about an hour and there's a drip bottle with a drug in it.

And so when you go with immunotherapy, and also there were some indications that maybe it was immunogenic, because there's a lot of mutations, but in any event, with our drug, 20% of people are cured by one or two injections of an antibody. The therapy, by the way, is you sit in a chair for about an hour and there's a drip bottle with a drug in it.

It's infused in your blood and you go home and that's it.

It's infused in your blood and you go home and that's it.

Yeah. And with blood, most patients, there's some scratchiness, there's some diarrhea, there's some...

Yeah. And with blood, most patients, there's some scratchiness, there's some diarrhea, there's some...

some stuff but usually nothing really better occasionally there can be bad stuff even you know patients some patients get type 1 diabetes which is an autoimmune condition and maybe they already had it borderline i didn't know it it just makes it worse but i mean there's a downside a lot of places most time it's not anyway it was 20 but then after we um

some stuff but usually nothing really better occasionally there can be bad stuff even you know patients some patients get type 1 diabetes which is an autoimmune condition and maybe they already had it borderline i didn't know it it just makes it worse but i mean there's a downside a lot of places most time it's not anyway it was 20 but then after we um

After our stuff started coming out, Tosco Hanzo in Japan, plus Arlene Sharp and Gordon Freeman at the Dana-Farber discovered this other checkpoint. C-24 was the first checkpoint. defined as a cell intrinsic, a molecule on the surface of a T cell itself that helps give a negative signal. So the T cell receptor obviously is a positive signal, it's the discharge switch.

After our stuff started coming out, Tosco Hanzo in Japan, plus Arlene Sharp and Gordon Freeman at the Dana-Farber discovered this other checkpoint. C-24 was the first checkpoint. defined as a cell intrinsic, a molecule on the surface of a T cell itself that helps give a negative signal. So the T cell receptor obviously is a positive signal, it's the discharge switch.

CD28 is the gas pellet, it's another positive signal. CD284 says stop all that stuff. It's time to quit. And so that's the one we chose to focus on was, you know, you can either make the other ones better. We chose, let's just take the brakes off. Let's disable the brakes. And it worked spectacularly well. As I said, it was a phase one trial, you know, which normally is just safety.

CD28 is the gas pellet, it's another positive signal. CD284 says stop all that stuff. It's time to quit. And so that's the one we chose to focus on was, you know, you can either make the other ones better. We chose, let's just take the brakes off. Let's disable the brakes. And it worked spectacularly well. As I said, it was a phase one trial, you know, which normally is just safety.

You make sure you're not killing anybody and then titrate it up until they start getting really sick and then back off a little bit. And that's the way that cancer therapy used to be. So there you prove it's safety. You find the maximum tolerated dose. How far can you go before you make people sick? I mean, you give that dose and you give it until all the tumor's gone.

You make sure you're not killing anybody and then titrate it up until they start getting really sick and then back off a little bit. And that's the way that cancer therapy used to be. So there you prove it's safety. You find the maximum tolerated dose. How far can you go before you make people sick? I mean, you give that dose and you give it until all the tumor's gone.

And if the tumor grows at all, it's a failure. All of that's out the window with immunotherapies. First of all, there is no maximum tolerated dose usually. People either, I mean, they may have adverse events, but you go up and up and It gets more frequent in the population, but people don't necessarily get sicker. It's not like there's a poisonous level of it.

And if the tumor grows at all, it's a failure. All of that's out the window with immunotherapies. First of all, there is no maximum tolerated dose usually. People either, I mean, they may have adverse events, but you go up and up and It gets more frequent in the population, but people don't necessarily get sicker. It's not like there's a poisonous level of it.

And in melanoma, in the first 14 patients, phase one, there were three whose tumors completely went away, which was just unheard of at the time, particularly in melanoma. because in 2011, when the phase one, phase three trial, sorry, that I was associated with was unblinded and reported to the FDA.

And in melanoma, in the first 14 patients, phase one, there were three whose tumors completely went away, which was just unheard of at the time, particularly in melanoma. because in 2011, when the phase one, phase three trial, sorry, that I was associated with was unblinded and reported to the FDA.

At that time, if you were diagnosed with metastatic melanoma, the median survival, 50% of people would be dead in seven months. Fewer than 3% would be alive at five years. After that, it was minuscule. It's not to say that everybody always died, but it was much less than 1% would survive. Now, with just this one drug, 20% are alive at 10 years plus.

At that time, if you were diagnosed with metastatic melanoma, the median survival, 50% of people would be dead in seven months. Fewer than 3% would be alive at five years. After that, it was minuscule. It's not to say that everybody always died, but it was much less than 1% would survive. Now, with just this one drug, 20% are alive at 10 years plus.