Researchers are working to develop new, more effective treatments for breast cancer. Dr. Adam Soloff joins the podcast to share his work on vaccines, including research funded by Susan G. Komen. This is part two of Dr. Soloff’s interview.
About Dr. Soloff
Dr. Soloff is a Susan G. Komen career catalyst researcher and the Assistant Professor of Cardiothoracic Surgery at the University of Pittsburgh.
Previously, he worked on emerging infectious disease teams at the University of Pittsburgh developing vaccines to treat HIV/AIDS, SARS-associated coronavirus, and avian influenza. Dr. Soloff is a graduate of the University of Delaware and the University of Pittsburgh School of Public Health. Amongst other roles and awards he was previously an Assistant Professor (Research); Department of Microbiology and Immunology, Medical University of South Carolina (MUSC) from 2012–2018 and was awarded the BD4BC Big Data Travel Scholarship, Susan G. Komen Foundation in 2019.
For more: http://www.ctsurgery.pitt.edu/person/adam-c-soloff-phd
Transcript
Adam Walker (00:53):
We’re all familiar with getting our seasonal flu vaccine, but understanding how vaccines protect us against viruses, like COVID-19, is something most of us aren’t familiar with. Dr Adam Soloff, a Komen funded researcher, has a background studying viruses, vaccines, and ways to develop better vaccines and therapies for viral infections. Throughout his research training, Dr. Soloff studied viruses such as HIV, SARS, and influenza, and their impact on the immune system to help demystify the world of viruses, vaccines, and how they are currently impacting our society. We’ve invited Dr. Soloff to speak with us today. Adam, welcome to the show.
Dr. Adam Soloff (01:34):
Hi. Thanks for having me.
Adam Walker (01:36):
All right. So before we dive in, give us an overview of, of who you are, what you’re doing, why we’re talking to you, and then, and then I’ve got a bunch of questions.
Dr. Adam Soloff (01:44):
Right. So I am a Susan G Komen career catalyst researcher. So that is a junior researcher, which is Komen has provided funding to launch you from kind of your mentor at state into an independent kind of a full fledge grown researcher. I started working with Komen in 2015 and the project which they picked me up for was to develop a vaccine that we could use to give an individual, give a person who has breast cancer that would hopefully give them this product, this vaccine, which would train their body’s immune system to fight off the cancer eliminated and essentially cure their disease. So we’ve been working on that for a number of years. In fact, that project just came to an end. And we started taking that different directions, trying to get things into patients now, trying to expand on it all in the right now we’re really interested in how we can use the body’s immune system to eliminate metastatic disease.
Dr. Adam Soloff (02:42):
But I think why you and I are talking today is I have a really weird background for a cancer researcher. I wasn’t a cancer researcher until about seven years ago. So I went to school, actually undergrad at Delaware, mostly philosophy, a little bit of science at the end. Came out, went to grad school and I ended up getting a PhD in infectious diseases. So my PhD was the grad school of public health at the University of Pittsburgh and that was in viral immunology. So for the first 12 years of like my mechanistic grownup working career, I was working on a vaccine to treat HIV and AIDS.
And during that time I was fortunate enough to work on some really cool vaccine projects. The first time SARS coronavirus came around in 2003 we developed a vaccine here at Pitt. And I was part of that team for that. And when bird flu came about again a couple of years later we were developing vaccines for that. So along the line, my thrust was to HIV, but then I had the fortune or the position to work on emerging infectious diseases as well. So most of my life I have been a viral immunologist and only a couple of years ago switched to cancer while working with Komen.
Adam Walker (04:00):
Wow, that’s fantastic. So, you know, viruses better than anybody. We’re dealing with viruses, we’re thinking about viruses a lot these days. What actually is a virus and what should people know about viruses?
Dr. Adam Soloff (04:13):
Yeah. that, that’s a good question. Literally, it’s a good question.
Adam Walker (04:19):
I feel like I should already know the answer and yet I, I’m asking the question knowing I don’t know the answer.
Dr. Adam Soloff (04:25):
Oh, I got a little lead. As I was tipped off of some of the questions I’d be asked. So what is a virus? And I started thinking about it. So on essence, a virus is kind of simple. So a virus is this little protein shell with a little package of genetics inside and the virus has to live inside a host cell. Normally we think about as you or me, you know, that’s our host element we’re interested in. Well that could be a cat, could be a reptile could be, you know, so virus gets inside a host cell, it makes more of itself then goes out and continues to spread. So a virus is not a living object, right? It is essentially this very simple structure and it replicates, it makes more of itself. And in the process, sometimes it gets you sick, sometimes it gets animal sick. But that question of what is a virus actually got me to thinking more like, why is a virus? I don’t know what evolutionarily that’s a different field beyond me is how they came about. You know, is it a purpose to just transfer a little bits of genetics here and there, but essentially viruses, really simple. A shell and a piece of genetics which has the potential to get you sick.
Adam Walker (05:37):
So, all right, so next simple question that I again recognize, I really feel like I should know the answer to this and realize I don’t have a good one, which is what are vaccines and how are they used to combat viruses?
Dr. Adam Soloff (05:50):
That’s great. And I don’t think that that you inherently should know. So our bodies are gifted with this wonderful immune system and our immune system all these white blood cells in our body are capable of detecting and attacking and gobbling up these threats, whether it’s a splinter or whether it’s a bacteria, whether it’s a virus, right? A vaccine is any way where we can in a safe manner, show your immune system that threat in the context that allows it to learn how to attack it. So some of the earliest vaccines, which are still some of the best are, let’s say a virus gets you sick. You can take that virus and kill it so maybe it doesn’t get you sick anymore and give it to the body and the body goes, Oh, okay, cool. That’s how that looks. That’s how this invader is going to look when it gets inside me. Your body recognizes how it looks and then if it’s exposed to in the future, you know, I come around in two weeks and sneeze on you with flu. Your body’s already has that built in response and already has that protective immunity where it knows how to fight and knows how to attack. So in a vaccine, what we’re doing is we’re taking something that might be really dangerous to you, you know, polio or flu or chickenpox, and we’re showing your body and I’m reopened in a safe way. Like, Hey, this is what these targets are going to look like when you see them. And if you see them, kill them very quickly, make sure that that doesn’t take hold.
Adam Walker (07:24):
Gotcha. I love that. Okay. That was helpful. So then let’s, let’s relate it to COVID-19. So there’s a lot of hope about a COVID-19 vaccine being developed and tested right now. I can tell us a little bit about how vaccines are created and what are the obstacles in developing a vaccine.
Dr. Adam Soloff (07:41):
Yeah, so I’m amazed. I mean, in the COVID-19 it’s, it’s terrifying. The impact on, you know, our health deeper into the society is really devastating, right? But as my nerdy scientists side, the fact that this is the first pandemic, this first, you know, serious outbreak that we’ve had globally in the internet age. So we’re getting information so fast, we’re getting information like left and right on things that before would take weeks, months, maybe weeks if you’re lucky, then more like months to get to you. And now we’re getting daily. Blessing and a curse because some of it’s good information and some of it, it’s not good information.
But the vaccine again, so the absolutely encouraging side is just the pace and the extent frame. So as of last week there were 78 vaccine candidates that were going to trial globally. I have no doubt…. I mean, I’m would be very comfortable putting money to say that some of those 78 are going to work just fine. Now with a 78, what’s different in this vaccine from that? Well, they’re all going to use part of that virus, right? To show the body’s immune system. So they’re going to say, okay, well here’s a target which we can show the body’s immune system that the immune system can learn to recognize and attack in a way that will protect you from future exposure. So something like Coronavirus, my kid has this spiky ball. It’s like a bouncy ball with little knobs on the front, right? So coronavirus is like, it’s got its protein shell and on the outside of it, you’ve got all these little knobs that stick up, right? Right. And those are called the spike proteins very aptly named.
Dr. Adam Soloff (09:19):
So it’s got all these spikes on it. What happens is the virus uses those spikes as kind of a lock and key mechanism when it comes in and finds one of the cells in your body that it wants to infect, that spike grabs on to a protein on that cell. So it has a receptor and those receptors are matched and then the virus can get into that cell, right?
What most everyone is doing are, they’re taking that spike protein and they are using an amazing amount of tricks and various sophisticated methods to basically show the body that spike protein in a very safe format, but also in a format that brings the alarm bells.
That says: “if you see this, you’ve got to attack this, right? And you’re going to attack it with everything you’ve got” You had to make, you know, antibodies and cells that will gobble it up and this and that. So that’s where, why do we have 78 vaccines? Well, because they’re all different formulations.
Adam Walker (10:14):
And throwing everything at it to see what works.
Dr. Adam Soloff (10:16):
You got it. I mean, I’ve reviewed a protocol a couple of weeks ago where one, the first one that went to trial was done in 42 days. I think that would be absolute science fiction two, three years ago.
Adam Walker (10:30):
Wow. So related to timeline, like what, what would you assume is the absolute fastest possible timeline for a COVID-19 vaccine versus what you think would be sort of a more average timeline for something of this nature?
Dr. Adam Soloff (10:44):
So I, I should preface this for everyone. One is that I am, you know, I do have expertise in experimental viral immunology and things like that, but I’m not an expert in the epidemiology..
I’m very cautious and I’m learning as much of this as it comes through as the rest of us are. But I think a year is reasonable. And actually pretty rapid compared to what we’ve seen. You know you can look at the recent Ebola virus outbreaks, which I think the last one we saw was 2016 and it still took a couple of years to really get something good and through testing. And the issue is that we need to make sure it’s safe. It’s not just, you know, safe and effective. There are two big challenges, especially with the coronavirus, which you have to consider. The first is that the population, which is really kind of the most at risk.
Dr. Adam Soloff (11:38):
They tend to be older individuals and they’re individuals with co-morbidities. So there are people who aren’t super healthy to start with, right. So they might have heart disease, they may have respiratory issues like COPD, they might be immunocompromised. So these are the individuals who are at the most danger, the most at risk of actually being affected by the COVID-19 are also the ones that are actually the hardest to prepare with the vaccine because their immune systems aren’t aren’t as robust. They’re not quite as strong, you know, so you got a healthy 20, 20, 25 year old off, you know, but somewhere that perfectly fits great, you know they’re easy. Right? Good immune systems. You know, it’s, it’s when you take like baby my father who’s a little bit more advanced in age and, and that’s the population that you need to protect with coronavirus that’s also the hardest to induce those immune responses into your system kind of wanes a little bit.
Adam Walker (12:38):
Okay. That makes sense. So next question, there’ve been some reports and theories that the COVID-19 virus may be able to mutate that that could lead to it coming back in the fall or the winter and having a resurgence. What does it mean to have a resurgence of a virus? And how do viral mutations influence things like vaccines?
Dr. Adam Soloff (12:57):
Yeah, so we’ll talk about mutation first. Cause that’s a, that’s the tried and true things that we know. It’s always easiest to talk about the things that we know. So if you take another virus, influenza virus, right? So most of us have had flu in our lives. No fun at all. You know, actually influenza itself is very, you know, is not without risk. It kills about 40,000 people in the US each year. But the flu bug is we talked about it as a protein shell that contains a little packet of genetics, right? Right. And the influenza and an incredible virus, that genetic code is made up of something called RNA, which is kind of the message. It’s like after you read the blueprint, that’s the translation and that gets made into all the structures. Right? Okay. So we have two events that happen. So one of the things is when viruses copied themselves, often the machinery that does that isn’t quite as good as the missionary that’s in you and me.
Dr. Adam Soloff (13:51):
So when they’re making the next, you know, the next line of viruses, sometimes they get a letter wrong. They got a little error here or there, right. Because you just want to make more of yourself. They don’t, you know, a couple of them get screwed up in the assembly line. You’re not really sweating that cause your job is to pump out more and more and more. Right. So every once in a while you get some that have a little bit of a, you know, factory defect. Right. Okay. So that means that that virus looks slightly different. So that’s what happens seasonally when like, so why is the flu different a little bit now than it was, you know, a couple months ago, right? Or you have a big flu, you know, you get ready for flu season and then by the end of flu season, people are getting it again. But sometimes you can have these little mutations that just change it enough to kind of get under your body’s immune system, get through the defenses.
Dr. Adam Soloff (14:39):
And the other event, which is actually more dangerous, is let’s say instead of just, you know, on the assembly line of making viruses, you just have a little air, right? And it causes this little screw up, this tiny defect. Sometimes they’re actually able to shift parts of this gene for that gene, right? And when that happens, you can have a big shift and now all of a sudden that that virus that’s created, it looks significantly different. And how do those mutations influence the actual vaccines themselves? So incredibly difficult to track, right? The first off, we don’t know how the Coronavirus will mutate yet, right? We know that there are changes that we’ve detected, but we don’t know if this will be minor changes that really won’t influence the development of a vaccine or if they’re major, if we take the flu virus, the influenza virus analogy, right?
Dr. Adam Soloff (15:32):
Each year as that virus circles the globe and flu kind of circles the glue with weather patterns. So each year is it circles the globe. It’s constantly getting these, you know, factory defects, these little mutations that occur so that by the time you see in the same region, the next year, the vaccine is much less effective, right? So for influenza, we have to develop a vaccine each year based on that formulation. And we hope that we get it right. We hope that the vaccine that we’re making at that we’re targeting this virus with is still effective and that virus still looks the same by the time it comes to us. Right? Right. It’s a constant battle about staying ahead of those mutations. Now when you get sophisticated, some of the vaccine development processes are trying to get at conserved regions to go, well, you know, and I like to think about when we were working in HIV, HIV is such a challenging virus because an individual has not treated every day, every letter of that viruses, genetic code will mutate.
Dr. Adam Soloff (16:33):
So every day you have the possibility to have, and I forget the number, but every possible change in that virus that can happen will happen.
Adam Walker (16:38):
Wow.
Dr. Adam Soloff (16:39):
So that’s why it’s been such a hard thing to pin down. What’s one way that we can get about that? Right? So some of the really cool techniques that people use are… I boil a virus down to a crunchy shell with a little bit of genetics in it, right? But let’s say you think about it like a dog. If we define a dog, a dog has four legs and a wet nose and a tail. Well, a virus has kind of the same thing. A virus has certain structural parts, right? They’ll have that crunchy shell. They’ll have a way that holds their genetic packets of a way to make more of that genetic packet. So some of that, if you’re like an HIV bug or a flu bug, you have to have those parts as basic parts, right? So more sophisticated vaccine strategies are finding ways to target those parts that make that virus survivors, right? So you target the tail cause every dog has a tail, right? And you just have to figure out how to target that part in the virus that is essential that you go, Whoa, Whoa. It can’t live without this. It can’t make more of itself without this. So it doesn’t have the ability to just, you know, completely mutate and change and look different. It has to kind of be that conserved region.
Adam Walker (17:50):
Right. Wow. Okay. So I think I might understand viruses now. I think I might’ve even say vaccines now. I’m still not sure I can fully verbally define them, but, but I’ve gained, I’ve gained a lot of understanding. So my last question for you is related to your Komen funded research. I know it involves developing a vaccine for breast cancer. Can you tell us the difference between a breast cancer vaccine and a vaccine for virus?
Dr. Adam Soloff (18:15):
Yeah, at the face value there’s almost nothing, but I think one of the challenges is …. so viruses are fairly easy to make a vaccine for because your body knows them as foreign. You know, if I stick influenza in you are this coronavirus your body freaks out. It knows that it should not be there. There’s like no part of you that looks like the coronavirus, right? So it starts to Mount this immune response to attack, attack, attack. It’s going to kill. So if you take that idea of how do we protect people with a vaccine or cure people with a vaccine in cancer, cancer has its own bag of tricks, which are really hard. So any cancer cell, you’re, you know, a memory tumor that memory tumor develops that came from healthy tissue. So at some point that was an individual’s own healthy body. And one of the problems there is your body doesn’t want to attack itself.
Dr. Adam Soloff (19:05):
It has this whole slew of checks and balances to not fight itself. Cause if you did, you’re going to develop autoimmunity, right? Right. Which could be anywhere from just kind of annoying and uncomfortable to like kind of fatal. So the default state of your body is to say, Oh, this is some of us. So we stand down. So when you go, “what are the issues with making a vaccine for cancer?” First and foremost, we have to combat the idea that we have to, in a very safe manner, say here are things that we can show the body that say, okay, here’s a target that’s on the cancer cell but not on a healthy cell. Right? Cause we don’t want to, we don’t want to attack and cause any collateral damage. But then we have to soup it up, right? So again, the body knows viruses, the body wants to fight and wants to kill a virus.
Dr. Adam Soloff (19:51):
But when we make a cancer vaccine, we just can’t say, okay, here’s a bit that’s on a tumor. Go get it. We need to encourage it. We need to help a lot. What we did with Komen is… well to back up one of my mentors, his mentor was a woman, brilliant lady named Dr. Olivera Finn. She discovered this region called MUC1. So this little flag that sits on the outside of his cell, and when a cell is healthy, the flag has all these sugars and looks like this beautiful Christmas tree. When a cell becomes cancerous, that little flag loses its sugars and looks like this naked twig – like a Charlie Brown Christmas tree. The body can tell the difference between the one that’s on cancer cells and the one that’s unhealthy cells. Okay? So what we did for Komen, we took her creation. So we took what she discovered. She found this target and I took a virus, which gives you a cold, nothing serious.
Dr. Adam Soloff (20:45):
It’s called an adno virus. Then we go in and genetically start tinkering with it. We chop out bits that allow the virus to make more of itself. So it’s just a dud. It’s a blank. And in those spaces, in those genes where we chopped out, we put that tumor target right? And then we put other factors to start souping it up, like immune hormones and different molecules that stimulate the immune response so that when we actually administer this cancer vaccine, the cells, the immune system sees that it’s a virus. They actually see that the shell that we put in. It’s kind of like a Trojan horse technique, right? Where the virus is, you know, sounds the alarm, the body goes, “that’s not supposed to be at an office and we’re going to get that.” But when it goes, it’s also making that tumor targets and they learned to kill the tumor in kind of the context of that viral alarm signals.
Adam Walker (21:36):
Wow.And the research that you’re doing just sounds kind of fantastic. So, thank you. Thank you for that. I really appreciate it. So I know we’re going to have another episode and we’re gonna talk a little bit more about vaccines and the roles they play in defending against viruses. But until then, do you have any final thoughts that you’d like to share with our audience?
Dr. Adam Soloff (21:53):
Okay, so I will leave on an optimistic note. People have tried cancer vaccines for years. I talk about my mentor’s mentor, Dr. Finn, who discovered this. She was putting the vaccines into starting in mice I think in the early nineties late eighties right? A long time ago. Why hasn’t it worked? Why don’t we have these now? And something that I’m just so excited about is that we’re at a point now where the technology of what we can do in the lab and then we talk about the pace of discovery, the pace of the inventions. You know, in the lab over here, we can read the genetic set of one cell. It’s craziness, but also the knowledge base that we have, you know, and we talk about why don’t we have a vaccine for cancer?
Dr. Adam Soloff (22:35):
Why isn’t there a breast cancer vaccine yet? And I think it’s on the horizon because of those two things. I think actually a lot of the vaccines that have been developed in generations past would actually work just fine if we also paired them with some better ways to boost the immune system. Or to maybe not sometimes boost the immune system, but sometimes attack that tumor’s ability to hide. Now when we talked a little bit about the body doesn’t want to fight itself, the body has all those mechanisms to not fight itself in seeing the tumor as itself. So all those mechanisms are in play. You know, the biggest breakthroughs in cancer in the past 10 years have been recognizing those immune mechanisms and starting to shut them off. So I think there are probably dozens of vaccines that would work over the past, you know, 20 – 30 years that once we pair them with those new techniques of shutting off the mechanisms that allow tumors to hide, I think are actually gonna work pretty well.
Adam Walker (23:34):
Fantastic. Well, Adam, thank you so much for joining me on the show today and we’ll have you back again for part two. So listeners, stay tuned for part two next week with Dr. Adam Soloff.
Sponsors
Support for real pink comes from Genentech, a member of the Roche group who pursues groundbreaking science to discover and develop medicines for people with breast cancer.
To find out more about Genentech’s latest research advancements, visit gene.com.
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