Tumor destruction and the immune response

20:31happens when we try to target tumors. >> Yeah. Right. Okay. >> Right. >> What happens? What happens to the immune response? Because this stuff doesn't happen in a vacuum in the body. You start messing with stuff. There's the police are going to come. >> There's a lot going on >> and be like, what's going on >> as we talk about a lot biology is uh not so simple. >> Yeah. So, we're going to we're going to jump start all the way to 2020. This is a paper um called non-therrmal hypotripsy tumor ablation promotes abscopal immune responses that enhance cancer amunotherapy. >> So it turns out that using these cavitation bubbles to take care of

21:12tumors actually o overpowers the immune response that is innate within the body. I think what's interesting too here just maybe taking a step back is you know amunotherapies are one tool in the toolbox right to combat cancer and tumors. What we're saying here is that by using this methodology of cavitation we're actually increasing the efficacy of our hammer. >> Yep. That we're using as a separate tool. And so there's this this this there's this increased correlation effect. >> Yeah. uh that it it it

21:53has a direct functional output. >> Yeah. >> But it also has this other benefit to other uh clinical therapies that we're using to solve in particular this issue uh around around cancer. >> Exactly. And and I want I want to talk about why that is cuz I was thinking like you know we've got the ultrasound therapies as what I was talking about right where you just heat up the tumor and then and then you burn it off. >> Yeah. Um, how come this is somehow better? >> Because so we have two things that both affect tumors structures >> and they both use sound ultrasound >> and they both use sound. But why is it that this >> this particular one is better? >> Okay. >> Well, it's that cooking versus disintegrating analogy that I was talking about. >> Um, with with the traditional ultrasound

22:35therapies, you heat up a tumor, right? And when you heat that up, >> that's going to burn off the tumor cells, the cancerous cells. Now, on the other hand, with this cavitation, you're going to break cells apart, but the components of those cells are still around. >> Yeah. >> And they're going to be available for immune recognition. >> You see what I'm saying? >> We're not deleting evidence from the crime scene. >> Yeah. We're not melting it. We're just like pulverizing it. But the immune cells can still that the police can still come and look at the evidence and be like, >> "Okay, >> I I probably should have been paying attention." >> Yeah. Yeah. Yeah. >> Right. But but you know what I mean? And so some of the components of those tumor

23:16cells that are broken down >> are tumor antigens. They're molecular features that an immune response is going to learn to target. >> On the other hand, if you just burn it off, those are now denatured proteins. The >> the the immune cells don't really know what they're looking at. It's it's the melted steel versus like intact stuff. Would would an analogy for this be we have undercover immune agents embedded everywhere >> when we burn them off the undercover immune agents when the immune response comes to the crime scene. >> Yeah. >> Right. They don't see them. >> Yeah. >> And so they're like our our undercovers are gone. >> Yeah. >> So we need to do something. >> Yeah. >> With cavitation we're saying the undercover immune agents, they may not

23:57be at the spot they were assigned to, but they're in the vicinity. And so they can still >> And there's like pieces of >> and and we can still be okay. Okay. This this it's still here. Yeah. >> And so I'm not going to I'm not going to overreact in my response. >> Yeah. But I'm at least going to learn what's going on here. I am going to heighten my response. I'm going to I'm going to like >> be more vigilant. That's a good distinction. >> You know what I mean? >> Yeah. Yeah. Yeah. No, that's a good Yeah. There. Exactly. Rather than being eviscerated from the from the scene, >> there's presence >> and you can then glean what your next action should be because there's some presence. >> Cuz a lot of the immune system are detectives, right? They're not just like like dumb beat cops. There's a lot of

24:38people that have like there's a lot of detectives that have memory that have the ability to to take antigens, recognize them for the rest so that if the tumor shows up elsewhere or something and that's something that we're going to get to. >> We got some immune Columbos on the scene. >> Yeah. Yeah. Yeah. Exactly. And so um this hystootripsy it's associated actually with the infiltration by innate and adaptive immune cells in the treated tumor >> including tumor reactive te- cell responses. So in the control you have just you know normal ablation >> and when you use hystootripsy the concentration of these T- cell receptors the CD8 plus

25:19T- cells they go up. This this is a >> the CD4 T plus T T cells like all of these guys that are like geared to learn about what the tumor is and make sure that that tumor does not show up elsewhere. It's going up. It it's it it it's it's so interesting because >> I don't know that this outcome is obvious >> you know but >> it's not I mean now that I think about it sure but like in 2000 when when or you know like five or however many 10 10 years ago when like this cavitation was being used >> not obvious at all I think and it's

25:59really it it's such a nice also because again we always talk about how there's a building block process to get to um ultimately something that is viewed as practical or functional for humanity. And it's like, hey, look, we have this new functionality. >> Just because you have functionality doesn't mean it has practical applications. >> Yeah. And this has more practical applications than what you even started out. I mean, you started out with just like why is the sound bad >> into okay, let's like try to burn a hole in the left ventricle >> to wait. This can supercharge cancer cancer therapies, >> right? Right. That that are already existing in what what folks who are

26:39dealing with this >> have to do. >> Yeah. >> To stand a fighting chance and you're basically saying, "Oh, yeah. Oh, by the way, >> it's going to make the thing you're already doing, which is is it's tough on the it's complicated. There's a lot, but it's it's going to make it more effective." That I I'm I'm just I did not expect that outcome. >> Yeah. I didn't expect this one either. And just one more figure from this paper. Yeah. >> Is um it shows that the effects on the tumors outside of the treated site. Okay. So you're treating with cavitation with this um hystootripsy in a certain spot and now you look at um pulmonary metastases. >> Mhm. >> Elsewhere. Okay. So so lung cancer

27:20happening maybe in the other lung or like there's a cancer happening here. Did it travel to the lung? Right. Um how is it moving out? because the immune response has been supercharged, right? The the ones that are treated with the hystootey versus the control night and day difference. The ones that are treated with hystootripsy have a much higher suppression >> of these pulmonary metastases. This is the the the the immune response sets up a tighter perimeter which then prevents the spread more than if it had not happened at all. >> Yeah. I mean this this is really really cool. I thought this was the most

28:02interesting conceptual turn you know and like a bubble cloud has become a biological instrument now right. It's in the first paper it was just like okay we want to remove tissue >> here the same kind of mechanical intervention >> can change the information available to the immune cells. >> Yeah. throughout the organism in the entire body. So this is like a definition of like >> a precise surgical tool that is doing way more than what we paid for. >> Way more than just the initial precise surgical outcome that you were looking for. >> That's right. So now we get to our