Cancer Immunotherapy

Dr. Rachel Brady sits down with our Host Dr. Michael Kent and talks Immunology and Immunotherapies in Companion Animal Cancer Treatments. 

Transcript

SPEAKER_00 0:00

We are looking at the gaps of where we still need to do better. And immunotherapy can help kind of fill in some of those gaps for some patients. Um, you know, and that's life-changing for the patients that it does help. And for the other patients, we have to keep working.

SPEAKER_01 0:18

Hello, and welcome to today's episode of Vetrospective, where we dive into all aspects of health and wellness for dogs, cats, and other companion animals. This is your host, Dr. Michael Kent. Immunotherapy has emerged as a whole new type of cancer treatment. Traditionally, we've used surgery, chemotherapy, and radiation therapy to treat cancer. More recently, we've added targeted therapies. These are drugs that target pathways that turn on really and get stuck and drive a cancer cell to reproduce. In both human and veterinary oncology, we now have the emergence of immunotherapy. Some early work was done in the late 19th century with something called Coolies toxins, but these we're not consistently doing and can cause a lot of toxicity. So this was before we even had an understanding of how the immune system works. Now, as we are really beginning to understand the cells of the immune system and how they interact with cancer, there are new treatments and even preventatives emerging. So today I have asked Dr. Rachel Brady to join us to talk about immunotherapy for cancer treatment. So Dr. Brady has an undergraduate degree in philosophy and then went on to do her veterinary degree here at UC Davis. She did her rotating small animal internship at North Carolina State and then her residency in oncology back here at UC Davis. So I've known her for a while. After finishing her residency, she then left and went to Colorado State to do her PhD in cancer biology, where she studied macrophages. We'll talk a little bit more about that later. I'm glad to say that Dr. Brady is now my colleague again. She was hired on at UC Davis as an assistant professor in oncology. So welcome, Dr. Brady. It's a pleasure to have you here today.

SPEAKER_00 2:06

Hi, thank you so much for having me. I'm really happy to be here today.

SPEAKER_01 2:09

And thank you for agreeing to do this. So I always like to ask people this. What got you interested in veterinary medicine and why specifically cancer? Why oncology?

SPEAKER_00 2:21

When I was a little girl, my grandmother gave me all of the James Harriet books. I don't know how many of our listeners will know those books, but they were a series of mostly true books written by a veterinarian. And I just thought they were the coolest thing ever. He got to travel around, meet all different animals, help all different animals, but also really helped people as well.

SPEAKER_01 2:47

All creatures great and small. I read those too.

SPEAKER_00 2:51

So that I really feel like I credit that with putting me on the path towards veterin.

SPEAKER_01 2:56

So you knew from a really young age.

SPEAKER_00 2:58

I did. I took a bit of a winding path, but I ended up here, yes.

SPEAKER_01 3:02

And why cancer?

SPEAKER_00 3:04

I didn't know I was interested in cancer until my last year of veterinary school, which is kind of called your clinical year, where you're actually in the hospital learning how to treat patients. And I realized how impactful the cancer cases are, not only to the animal, but almost any person you meet has a story of having cancer or knowing someone with cancer. And that really kind of got me interested in how much work there is to do in that field and how much potential there is to help.

SPEAKER_01 3:38

That's that's cool. Mine's a little similar. We'll talk about maybe that some other day. So um maybe to start out, cancer is a very, you know, big term. Can you try to define for me or tell me, you know, what is cancer?

SPEAKER_00 3:55

Yeah, I'm glad you asked that because I think to understand how immunotherapy works, it is important to understand how cancer evolves in the body. Um, and so if you think of a normal adult human or adult dog, we have trillions of cells in our bodies. And each cell has DNA in it, which you can just think of as a recipe, but it has billions of letters making up this recipe.

SPEAKER_01 4:23

It's a complex recipe.

SPEAKER_00 4:24

It is. So if you think of that, we have trillions of cells with billions of letters inside of them. And every time a cell needs to duplicate or or make another cell of itself, it has to copy all of those letters perfectly. And so I bring that up to say over a lifetime there's going to be mistakes made.

SPEAKER_01 4:44

It's like typing, right? You know, if you're typing and you're just typing words from another paper, you should see my autocorrect, right? It's not good.

SPEAKER_00 4:53

And so even though our body has evolved ways to correct those mistakes or avoid those mistakes, it's inevitable that mistakes will happen. And when enough of those mistakes accumulate at a certain point, that we call that cell cancerous.

SPEAKER_01 5:10

Okay. And then that cell divides and that leads down the road to having a mass we can find and then, you know, and the like. So Right. What I was also saying now as we go here, kind of the big question. So why doesn't the immune system just kill this cancer cell like we would any virus, bacteria, or other infection that we're faced with every day? We have thousands of bacteria or viruses around us.

SPEAKER_00 5:37

Right. And that is the big question that everyone's trying to figure out.

SPEAKER_01 5:41

That's why I asked you.

SPEAKER_00 5:43

But um, so I think to understand that, we need to understand how our immune system works. Our immune system is made up of cells we call white blood cells, and their job is to keep our body in homeostasis.

SPEAKER_01 5:59

So it's homeostasis. What do you mean?

SPEAKER_00 6:01

A state of balance.

SPEAKER_01 6:02

Okay.

SPEAKER_00 6:02

We can't have too much of any one thing. So when anything disturbs that balance, as you mentioned, an injury, an infection with a bacteria or a virus, it's those white blood cells that identify that and respond to it. I like this metaphor that I've been told. I did not come up with this myself. You can think of all these white blood cells as having satellites on them. We call them receptors, but they're basically the same thing as a satellite sticking out from the cell, and they're constantly patrolling the body for anything that disturbs this balance. And when they send something, they start sending sending signals, just like a satellite sends signals down a big cable. They send big signals inside the cell, which then tells other cells that something is going on. And these cells need to react to fix the problem.

SPEAKER_01 6:58

Okay, okay. Yeah. So we're trying to fix this problem here. And so why don't they with cancer cells?

SPEAKER_00 7:05

So what happens with cancer is two different things. First is, as we already mentioned, these cancer cells are actually our own cells that have small mistakes in them. And for some cancer cells, our immune cells just literally cannot recognize that they are something that's disturbing the balance because they're not so foreign as a as a virus or a bacteria that's invaded your body.

SPEAKER_01 7:33

So it's your cell that's changed. So the immune system says, oh, that's your cell, so it doesn't attack it.

SPEAKER_00 7:39

Right.

SPEAKER_01 7:39

Yeah.

SPEAKER_00 7:40

The other main thing that happens is that unfortunately the cancer cells can be very smart, that they have evolved ways to basically build a brick wall around this mass or this tumor that's growing and basically hide it from the immune system. So even if our immune cells could try to recognize them, they're often blocked from doing that because the cancer has outsmarted them.

SPEAKER_01 8:07

So there's this concept of immune editing. I'm wondering if you could explain it better for me and for everyone who's listening.

SPEAKER_00 8:14

Right. So immunoediting is broadly the process by which these cancer cells escape our immune system. So as I said, all of these white blood cells are constantly on alert for anything abnormal in the body. So there's an early phase when cells with these mistakes, maybe we'd call them precancerous or very early cancerous cell, that our immune system is recognizing them and eliminating them. And that's happening in all of us all the time.

SPEAKER_01 8:47

Every day.

SPEAKER_00 8:48

Every day. So the immune system and the cancer cells are in an equilibrium state, then where not one of them is winning.

SPEAKER_01 9:07

Kind of like a chronic infection in a way.

SPEAKER_00 9:09

Exactly. And at that point, usually none of us know that a tumor is there. That's usually before we're able to detect it on most of our tests. And then the third, the third step is unfortunately what we call immune escape, where the cancer cells has have evolved enough of these mechanisms to outsmart the immune cells and build up that brick wall. And it kind of tips that balance over into letting the tumor grow, what we call in an uncontrollable fashion. And that's really the hallmark of cancer by definition, that it has escaped the ability of our immune system to control it.

SPEAKER_01 9:46

So this is almost Darwinian in the evil kind of way that basically it's survival of the fittest cancer cell. Exactly. Yeah, that's that's very cool. So when we're talking about these walls and the like, are we looking at basically immunosuppression? Yes. And are we looking at it in the tumor or your whole body? Are you immunosuppressed?

SPEAKER_00 10:07

Yeah, that's a great question. So we once a tumor has grown to that stage where it's escaped our immune system and this is the time that we can start picking it up or it might start causing symptoms, it has developed its own environment, like its own little ecosystem. And in that ecosystem, it is um, there's a ton of immunosuppression. So it is keeping out the white blood cells that we would want to be in there to kill off the abnormal cells. And and which we can talk more about later, it is recruiting our body's own immune cells to actually help it to grow. So it's almost flipped these cells that are supposed to be helping us to the bad side.

SPEAKER_01 10:51

And I always also like to just think of it in a terms of so we almost need autoimmune disease to kill those tumors. So they're using that side, that balance of the immune system that's keeping us from attacking our own body, but amplifying it.

SPEAKER_00 11:12

Yeah, exactly. Exactly. And uh you can almost think of autoimmune diseases as the flip side, where we mentioned before a body needs to be in balance. And autoimmune disease is where the immune system is way ramped up and attacking itself. Whereas cancer is, you're absolutely right, it's stopped attacking itself when we would want it to.

SPEAKER_01 11:33

Yeah. So can you tell me what are the main types of immunotherapy that we use to try to treat and maybe just keep in mind how we're trying to change that environment? I know this is an area you do research in.

SPEAKER_00 11:49

Yes, definitely. So as we've learned more about these immune cells and our immune system in the past couple of decades, we have realized that we can try to convince the body's immune cells that it should be fighting these cancer cells. And there's um two main ways you can do that. One is to try to damage that brick wall I've mentioned a couple ways. So you can knock it down in different ways or weaken it.

SPEAKER_01 12:18

So this brick wall that's kind of isolating the tumor and keeping it immunosuppressed.

SPEAKER_00 12:23

Correct. And a very popular example of doing that is um our checkpoint inhibitors, which some people may be familiar with. But all that a checkpoint inhibitor does is stops the cancer from being able to build up that brick wall. It's removing its ability to do that. So then our immune cells would can flood in and start killing those cancer cells.

SPEAKER_01 12:46

So this is kind of like inhibiting the immunosuppression.

SPEAKER_00 12:49

Exactly.

SPEAKER_01 12:50

Okay, taking off that break that's stuck on that's keeping the cancer basically protected.

SPEAKER_00 12:58

Yes. It's uh inhibiting the inhibitor. And this has been life-changing for people with melanoma or some types of metastatic lung cancer. It has literally turned fatal cancers into ones that can be cured or controlled really long term.

SPEAKER_01 13:12

So I interrupted you. You said there was two types.

SPEAKER_00 13:14

So yeah. So the other way that people try to um approach this is rather than weakening this metaphorical brick wall is just to overwhelm it. So to really strengthen our immune response to the point that um this brick wall doesn't even matter. We're just we have so much of an immune response, it can flood in there anyway. Um, and so some examples of that are things like cancer vaccines, which is not a vaccine how a lot of people think of it.

SPEAKER_01 13:47

Um so do you mean like a preventative vaccine or more of a treatment vaccine?

SPEAKER_00 13:53

More of a treatment vaccine in this case, where we are trying to help our immune cells know which cells to attack. So a normal vaccine might tell your cells, hey, these proteins look like they come from the flu. If you see these flu proteins in your body, you need to attack them. We can do the same thing, but with um pieces of the cancer.

SPEAKER_01 14:16

Great. So basically, instead of me going to get my flu vaccine every fall, you might, would it be your own cancer cells I would use to do this, or more of a generic vaccine like you get at a pharmacy?

SPEAKER_00 14:30

People have tried both both approaches. It is trending more towards personalizing these vaccines for an individual tumor. Another really popular strategy that some people might have heard of for this idea of just kind of strengthening the immune response so much that it overwhelms the immunosuppression are CAR T cells. This is one of the earliest immunotherapies to be incredibly successful.

SPEAKER_01 14:59

And this is when we just And this is in people still at this point.

SPEAKER_00 15:02

This is in people, although there's several early trials in dogs as well.

SPEAKER_01 15:07

And can you tell me what is a CAR T cell? Because that's yeah, you know, it's a little complex, right?

SPEAKER_00 15:13

To answer that, just to define a T cell first, is we've been referring to the immune system as white blood cells. Very generally, though, those white blood cells are split into two groups. There's the initial kind of guards that we call the innate immune system. And those cells are able to recognize a virus or a bacteria or maybe those early cancer cells right away and kind of stimulate a fast response, but it's a very nonspecific response. It can kind of try to wipe out anything, but it's not targeted against a specific virus or a specific bacteria.

SPEAKER_01 15:53

Okay.

SPEAKER_00 15:54

But then what it does is also signal to the body that we need to mount up this secondary set of defenders. And this is called the adaptive immune system.

SPEAKER_01 16:05

And that's what we vaccinate with, or that's the response we're trying to get.

SPEAKER_00 16:08

Exactly. So one of those cells that's very important is the T cell. It's a white blood cell that's main job is to kill cells that shouldn't be there. So when we say a car T cell, that fancy um word in front, the car, it's an acronym just for chimeric antigen receptor, which that's not important. The important part to know is that we take a person's or a dog's own T cells out of their body, we modify them in the laboratory and tell it, hey, you need to be looking out for this particular type of cancer cell. And then we put them back in the body in huge numbers, hoping that they will attack the cancer cells.

SPEAKER_01 16:51

So basically you just reprogram them so that they find the target that you wanted to, in this case, the cancer.

SPEAKER_00 16:58

Exactly. Yeah. And um CAR T cells have been life-changing for people with different lymphomias, lymphomas and leukemias. And those are cancers that are we call kind of bloodborne, that are mostly found in your blood. And they have changed certain types of lymphomas from, again, fatal into being able to be cured.

SPEAKER_01 17:18

So you've been talking about some of these as advances in humans. And I know we're a bit behind, but can you explain to me or tell me a little bit about how similar our immune systems are between, let's say, a dog or cat and a person? And can we just use an immunotherapy made for people? So can I take one of the treatments and put it right into a dog or a cat?

SPEAKER_00 17:46

Yes, great question. Because obviously I'm a veterinarian and my passion is helping animals.

SPEAKER_01 17:52

Mine too.

SPEAKER_00 17:53

But as I've mentioned, I really love the opportunity to also help people. Um, and that is the really cool thing that dogs and people and cats actually develop very similar cancers. So it's not perfect, they're different species, but a lot of the tumors that they develop are similar enough that breakthroughs that we find in a dog can be applied to a human and vice versa.

SPEAKER_01 18:18

Yeah.

SPEAKER_00 18:19

It's not perfect. Immune systems are complex.

SPEAKER_01 18:24

And so are immune systems similar?

SPEAKER_00 18:27

More similar than a lot of the animal models that have to be used. So anytime a new immunotherapy or any drug for that matter is going to be given to people, it has to be shown to be safe. And that has been historically done in mice. Mice have very different immune systems from people.

SPEAKER_01 18:47

Yeah.

SPEAKER_00 18:48

So while dogs and cats are not perfect replicas of the human immune system, they're a lot closer to us than mice.

SPEAKER_01 18:55

I like to think of myself more like a dog than a mouse.

SPEAKER_00 18:59

Yeah, me too. And and it is, it really does go both ways. We can really help all of those species by collaborating with our colleagues who treat people. Breakthroughs that they've had can help us treat dogs and cats and other animals better, and vice versa. And that is one thing I really love about what we do.

SPEAKER_01 19:20

It's pretty neat. So one of the areas that has been a huge breakthrough for, like, example in lymphoma and people is something called a monoclonal antibody.

SPEAKER_00 19:30

Yes.

SPEAKER_01 19:30

I was hoping you could kind of maybe break that down for me, explain what it is, and then kind of, you know, we'll go from there.

SPEAKER_00 19:38

Yeah. Yeah. That is another big area of research in immunotherapy. So antibodies in general are a protein made by another immune cell in our body, and they are an important way of also killing off things that shouldn't be there.

SPEAKER_01 19:54

So when a bacterial infection or something like that.

SPEAKER_00 19:58

Exactly. Some of our immune cells will produce massive amounts of antibodies that in a bunch of different ways can kill off those bacteria cells. Bacteria, viruses, et cetera. Exactly.

SPEAKER_01 20:08

So how are we trying to use them for cancer?

SPEAKER_00 20:10

So you can, in a lab, make these antibodies that target the proteins that a cancer cell puts out. So basically everything in our body, everything that we're talking about, it revolves around proteins. Proteins are the things that we can tell these cells to fill.

SPEAKER_01 20:28

They're a building box, right? They're proteins make up everything in us. Exactly. So are there enough differences between a cancer cell with a protein and a normal cell with a protein? Or are you just going to make one of these really bad autoimmune diseases we were just alluding to earlier?

SPEAKER_00 20:46

Sometimes.

SPEAKER_01 20:47

Yeah.

SPEAKER_00 20:48

Not all the time, but some specific types of tumors have enough of these um mistakes that we've talked about that they're making proteins that are very, very different from normal proteins in our body. And we can target target those.

SPEAKER_01 21:02

Great.

SPEAKER_00 21:03

Some tumors, we're not as lucky and we have to use other approaches.

SPEAKER_01 21:07

So can I take there's a lot of monoclonals available for people now. You probably see them advertised on TV all the time. Yes. And they all end in MAP. Yep. Right. And they're using them not only for cancer, but I've I've seen an ad for eczema and other things as well. So can we just take those and use them in our patients now? Can I use it in one of my dogs or cats? I know that's a loaded question.

SPEAKER_00 21:29

No, that is a good point because that would be awesome if we could.

unknown 21:32

Yeah.

SPEAKER_00 21:32

But unfortunately, what happens if you take one of these antibodies targeted towards something in the human body and put it in a dog body, the dog's immune system is going to say, Whoa, there is something foreign here. It's going to know that that protein doesn't belong there and attack it or make other antibodies to attack it, just like it would any other foreign invader. So what we need to do is make the protein. Proteins make these antibodies very similar to the natural antibodies a dog's body might make or a cat's body might make. However, it's still very helpful. We can still use a lot of the foundational work, but we have to just make it specific to a dog's body or a cat's body.

SPEAKER_01 22:18

Are some tumors more likely to respond to immunotherapies than others?

SPEAKER_00 22:22

Yeah, this is an interesting question. It has become more normal to talk about some tumors in the immunotherapy world as hot or cold.

SPEAKER_01 22:33

And what do you mean by hot or cold? What's a hot tumor?

SPEAKER_00 22:37

So a hot tumor has a lot of these proteins that are really different and that we could really attack well. While a cold tumor, you can think of it, we say cold, but you can think of it as, yeah, this kind of bleak winter landscape, just without a lot of things going on that we can really target with our immunotherapies.

SPEAKER_01 22:56

So what give me an example of a hot tumor?

SPEAKER_00 23:00

In people and in some versions of the dog tumor, melanomas are what we consider a hot tumor. And that means as they've been replicating, as they've been like making new cells and all these mistakes are accumulating, they are very, very different from a normal cell. And so it is much easier to target that with some of these things we've been talking about.

SPEAKER_01 23:23

So that's why it's the prototypic, you know, poster child for immunotherapy in some ways, and some of the big advances have been made. So can you give me an example of a cold tumor that we see in VetMed?

SPEAKER_00 23:35

Yeah, unfortunately, in both um children and in dogs, there's a type of tumor called osteosarcoma that grows in the bone. And unfortunately, it does affect um younger children. And that tumor is kind of known for being very cold, where it's been proven very hard to target with immunotherapies because there's not a lot of things for our immune cells to latch onto on it.

unknown 24:00

Yeah.

SPEAKER_01 24:01

So I told everyone earlier that you like to study macrophages. At least you did your PhD in it. Yep. So first, what's a macrophage? That's besides something with a cool name.

SPEAKER_00 24:14

Yeah, I've been waiting for this. I've spent the past four years uh talking about these cells. But so we did briefly mention these two different arms of our immune system, where we have that initial wave or the innate immune system, and then that second wave that's a little bit later, the adaptive immune system.

SPEAKER_01 24:33

That initial assault to try to knock something out. Right.

SPEAKER_00 24:37

Most of the immunotherapy work so far has been on T cells, which are part of that second later wave of our immune system. But more recently, in the past decade or so, we've become interested in these cells that are part of that innate wave. So innate meaning they're the first responders, sometimes within hours, of some type of insult, of an injury or an infection. One of those cells is called a macrophage. A macrophage are these big cells that's main, their main job is to eat other things in the body.

SPEAKER_01 25:08

They kind of clean up the mess, right?

SPEAKER_00 25:10

That's right. They can clean up, they can clean up viruses, bacteria, they can clean up our own cells that are dead or diseased. And we can convince them to sometimes eat up the tumor cells.

SPEAKER_01 25:24

So how do we do that? Well, that's the million-dollar question, right?

SPEAKER_00 25:27

That's right. So one thing that cancer does, as we've mentioned before, but really particularly with macrophages, is it convinces macrophages to support it. So part of that brick wall I've mentioned, that is chock full of macrophages that are defending the tumor from other immune cells from coming in. And they are directly kind of helping the tumor grow. So what we needed to figure out is how do we convince them to get back on the good side?

SPEAKER_01 25:58

We have to reprogram, get them out of the cult.

SPEAKER_00 26:01

Absolutely. And we call that re-educating or repolarizing them. There's many different ways to do that, but the the main goal is to remind the macrophages, hey, you're actually supposed to be fighting against these cancer cells instead of defending them. And the cool thing is that the macrophage-based therapies are not really meant to be used alone. What they're meant to do is be used in conjunction with some of these long-standing therapies at work, like checkpoint inhibitors, and they make each other more effective. So think of this, you know, this brick wall surrounding the tumor, and you're weakening it at certain points with these checkpoint inhibitors. But if you can also then um, you know, change a bunch of the macrophages in that brick wall and say, okay, you also attack the tumor. You've weakened it in more than one way. So, really, when you can use these therapies together, they tend to be synergistic.

SPEAKER_01 26:55

This is great. Now, I'm gonna pretend to be a cynic, which I'm not. I'm an ecologist, so therefore I'm an optimist. But over my career, I've seen cancer cured many, many times in the headlines.

SPEAKER_00 27:08

Yep.

SPEAKER_01 27:08

And then we come back to the reality of what it can do. So these immunotherapies that are emerging, they're not all here yet for us. But where does this fit in? How do we how do we integrate it into our practice? How do we bring these therapies forward? How do we know if they work?

SPEAKER_00 27:26

Right. That's a that's a good point because obviously I'm passionate about this and I'm painting this awesome picture, which is full of it is really there is a lot of room for hope or a lot of reason to hope. But um, like anything, it's not perfect. We don't have a precise controller of our immune system. So there's still side effects to these therapies, and there's still a lot of patients who maybe respond to them for a short time and then the tumor starts to grow again, or don't respond at all, or have such bad side effects they can't, they can't continue on with the treatment. And so I know a lot of people always ask me, you know, why don't we have a cure for cancer yet?

SPEAKER_01 28:07

Yeah.

SPEAKER_00 28:08

And it's because every single tumor that grows is different. So we're not trying to cure cancer.

SPEAKER_01 28:12

We're trying to, you know, cure a million different diseases.

SPEAKER_00 28:17

Exactly, as they keep popping up. And so what I think is this is not going to um wipe cancer out. But what we we are looking at the gaps of where we still need to do better. And immunotherapy can help kind of fill in some of those gaps for some patients. Um, you know, and that's life-changing for the patients that it does help. And for the other patients, we have to keep working.

SPEAKER_01 28:41

And how do we work? How do we figure that out? How do we know if it works or not?

SPEAKER_00 28:45

Yeah. So um, one thing that you and I are both involved in are a softball question, I know. Clinical trials, which is really important because um we want to, in a, you know, in a scientific way, show that these therapies are safe and then show that they're effective. So um, both in people and in dogs and in cats, um, we run these very controlled trials where we enroll, you know, let's say dogs with a specific tumor type, give them a specific treatment, and um very rigorously kind of follow how they do. And it's cool here at UC Davis. Um, some of the people here made their uh made our own checkpoint inhibitor that you were involved with.

SPEAKER_01 29:34

Yes. Yes.

SPEAKER_00 29:35

And and that's a huge deal for us because that's been used routinely in people for for decades now. And so we need to really work to catch up to that. And we're giving it to dogs now with with diseases that are considered very end stage and would be um this these cancers would be killing these dogs within a short period of time.

SPEAKER_01 29:52

And we've had our first dog actually clear its lung tumors, which is pretty amazing.

SPEAKER_00 29:57

It is amazing.

SPEAKER_01 29:58

Yeah, so this is a lot of hope and a lot of promise. I mean, that's what we need in oncology, right?

SPEAKER_00 30:03

Yes, absolutely.

SPEAKER_01 30:04

So I'm gonna wrap it up here. And um just wanted to say thank you for taking the time to speak with me. It's been a pleasure, Dr. Brady.

SPEAKER_00 30:14

Oh, yeah, thank you for having me. I hope I hope it was useful to everyone who's listening.

SPEAKER_01 30:18

I hope so too. You know, I think immunotherapy is just this black box right now, and I hope kind of our deep dive into how it works will be helpful in understanding that.

SPEAKER_00 30:28

Yes, absolutely.

SPEAKER_01 30:29

All right, thanks.

SPEAKER_00 30:30

Thank you.

SPEAKER_01 30:33

The vetrospective, as with life, takes a village. I want to thank those who suggested I start this project and everyone who has encouraged and supported me along the way. Particularly I want to thank our producer and director, Danae Blythe Unti, Nancy Bay, who is our program coordinator, our sound mixer, Andy Cowett, and theme music was composed and produced by Tim Gehagen. Thank you all, and we'll see you next time.