Melanie Cole, MS (Host): Welcome to the podcast series from the specialists at Penn Medicine. I'm Melanie Cole, and today's discussion is focused on research and treatment for autoimmune diseases at the Colton Center at Penn Medicine. Joining me is Dr. John Wherry, he's the Director of the Colton Center for Autoimmunity at Penn Medicine.

Dr. Wherry, thank you so much for joining us today. There are around 80 to 100 known autoimmune diseases. I mean, this is a big topic. Afflicting an estimate of 24 million Americans. These are big numbers. That said, there's far too little attention paid to autoimmune diseases, so let's start with the bigger picture.

What are they? For providers that really hear this term, and it's a catch-all umbrella term, speak about autoimmune diseases in general, and why there's suddenly such a focus on it. I mean, it even feels like celebrities are now talking about their autoimmune diseases.

John Wherry, PhD: Yes. Well, thanks for having me today, Melanie. It's just a really important topic and let's start with just a sort of general level set and framework for things. Autoimmunity or autoinflammatory diseases are when your immune system, which is typically charged with keeping us safe from and, in some ways, keeping our tissues healthy, turns on itself and starts reacting to parts of your body that it's supposed to ignore. And depending on what part of your body, that can lead to different forms of autoimmunity, whether it's affecting your joints, as in rheumatoid arthritis, or your intestines, as we see in things like inflammatory bowel disease. You can see your immune system basically attacking yourself. And so that's what we talk about when we think about autoimmune diseases.

And you can see these manifest in many different ways. But I agree, it does seem like we're talking about this much more frequently these days, and these are large numbers, 24 million people by some estimates. If you use a little bit broader definition, you may get as many as 50 or 75 million Americans affected.

I think there are a couple of  reasons why this seems to be a major topic these days. One, over the past decade or so, we've had incredible successes with using the immune system to treat cancer. This means that we're understanding more and more how to use the immune system as a drug and how to turn the immune system to do jobs that we want it to do.

At the same time, we've seen advances in new drugs for autoimmunity. New classes  of drugs, have come to market. They're having really important effects in patients with autoimmunities. You see ads on TV for many of these, these days. And I think the third component that we shouldn't ignore is that we have a, perhaps a newfound appreciation, to say it one way, for the immune system over the past five years.

And nothing makes the public appreciate the fact that they have an immune system than a pandemic where we have to depend on our immune system to keep us healthy from infection, with COVID-19. So, I think the combination of these has had us realize what autoimmune diseases are and pay more attention when people, celebrities, neighbors, relatives talk about their autoimmune diseases.

Host: Dr. Wherry, tell us about the Colton Center for Autoimmunity. Tell us about its mission, the research that you're undertaking, and the role Penn Medicine and the consortium play in the future for diagnosis and treatment for patients.

John Wherry, PhD: Our mission for the Colton Center at Penn is to revolutionize how patients with autoimmune diseases are diagnosed, treated and cured through collaborative, transformative, and translational science. So, what we really mean by that is we really believe that when we understand the mechanisms underlying autoimmune diseases, we can actually apply that information in near real-time to lead to better treatments and, ultimately, cures of autoimmune diseases.

We mean this because we've shown that we can do this in other diseases. We can use the immune system to actually enable better treatments and better cures of the patients with lots of different diseases. So, the way we're doing this is we're really using, the way we're treating patients every day with autoimmune diseases to learn mechanism. We're capturing samples from patients when they're being treated with typical drugs, with new drugs, and learning from their response to existing therapies, both when they work and also when they fail, so that we can understand what the gaps are, design better therapies to bridge those gaps and move that information back into the clinic as quickly as possible.

So we're doing this based on a really, I think, novel principle that the immune system is our new drug. Cells of the immune system survey and monitor every tissue in our body all the time. They do that, and they actually can tell us what's happening in those different sites. And, if we use that information appropriately, we can actually guide the immune system to redirect, rewire itself, and redeploy its immune mechanisms to reverse autoimmunity and not just treat symptoms, but treat for cures.

Host: That was excellent. So as we look at this picture there's so many autoimmune diseases now. Are we looking towards a cure? And how can we look to a cure for one that won't then trickle down to all the others?

John Wherry, PhD: Well, this is a great question, and I think one that we as researchers ask ourselves all the time. And we often compare autoimmune diseases to cancer, and that's both useful, and also kind of misrepresents the problem. So, cancer is not one disease. But we think about cancer as a single entity because we've had a war on cancer or we have a National Cancer Institute.

But it's very different if you have melanoma or you have pancreatic cancer or brain cancer. Those are not the same disease, even though we all talk about them as cancer. You can think about that the same way for autoimmune disease. Rheumatoid arthritis is not the same as inflammatory bowel disease. Those are not the same as a skin disease like psoriasis. Now, the difference here when we think about cures is autoimmune diseases; we don't think about these as terminal diseases like cancer. So, the stigma about needing a cure is very different. And that's probably not fair to autoimmune diseases, some of which can be really devastating, can lead to early mortality.

And so we should be thinking about them as needing that focus on cure. But we don't. Many autoimmune diseases are things that we manage. We treat the symptoms; we try to ameliorate the effects of the autoimmune disease and the discomfort of skin rashes or joint pain, or, you know, intestinal discomfort.

But we need to be moving towards cures. And to do that, we're working very hard to get at the fundamental mechanisms. We need to go back earlier in the disease process to try to turn off that immune response that's attacking ourself or redirect it in some way that actually leads us to drugs that are not just treating the symptoms but are actually treating the causes and getting to the cure.

So, this is a major focus of our autoimmunity center at Penn and a major focus of our efforts in the research side of understanding autoimmune disease.

 Dr. Wherry, you've mentioned cancer, and certainly there is a lot of awareness and a lot of research funding. By comparison to the NIH funding for cancer research, funding for autoimmune disease research is lagging. Why is this, and what role might private philanthropy play for making up for what's lacking from governmental sources? Do you think that private funding for research would offer advantages that are not possible with government funding?

John Wherry, PhD: That's exactly right. So, again, I think, starting with sort of a few facts and figures is often helpful. There are about 16 million cancer patients in the U.S. We spend about 8 or 9 billion dollars in federal funding for cancer research every year. By comparison, there are about 25 to maybe 50 million autoimmune patients in the U.S.

So, maybe twice as, maybe two and a half times as many autoimmune patients. And we spend 1 billion in federal funding. So, 1/8th to 1/9th of the federal funding for autoimmunity for a disease that's much larger or a set of diseases that affects a larger number of people.

So, we are disproportionate. And again, part of that is the stigma of cancer, which is changing. But part of that is our decentralized way of funding autoimmune research with our federal mechanisms of supporting biomedical research. Cancer has the National Cancer Institute, which is a single entity that funds most of cancer research in the United States.

In contrast, autoimmune research is funded through, there are 27 different Institutes at the National Institutes of Health, and many of them fund autoimmune research. So it's not as nearly as well coordinated as for cancer research. So that's one reason. A second is that it hasn't received the public attention that cancer has.

Remember, Richard Nixon announced the war on cancer fifty years ago. And so we've had 50 years of a concerted effort, of a real targeted approach to make cancer go away. And while we've made great strides to that, it's been a 50-year battle to do this. The coalescence of attention on autoimmune diseases is really very recent.

And so we really are just getting started. Even though these diseases have been here for as long as we've been practicing modern medicine, our ability to coalesce them into a single entity that deserves our attention is actually fairly recent. Otherwise, they've sat in their separate, sort of small silos of individual diseases that haven't had the collective benefit of one umbrella term. 

That's one big part of it. So, there's no question that government funding, NIH funding, is the single biggest driver of discovery. It's the point origin for all new drugs that get developed, even though those drug discoveries made with NIH funding get turned into the foundation for drug development, most often in the private sector.

It's really important that we complement this system with other sources of funding. Philanthropy is critical. It gives us the ability to focus our attention on diseases of high unmet need. Diseases of particular gap where clearly the federal system isn't working well enough. It allows us to do some other things that are really, really important.

When scientists have a great idea and want to apply for federal funding to make new discoveries on a particular autoimmune disease, it's about an 18-month to 2-year cycle before, if you're lucky, a single dollar is seen for that research. It's about six months of writing an application. You wait about another six months before that application is reviewed. You get a score. Only the top about 8 percent of applications are funded. Most often you have to resubmit for another cycle, inching your way up that funding score ladder until something around 20 percent of the time things get funded. That's too slow for many diseases and people who are suffering.

So philanthropy often allows us to short-circuit that system and move much more quickly in areas where there are unique opportunities. The, for example, AI revolution is not going to wait two years for federal funding to apply these novel technologies to new drug development.

  need to do it now. Philanthropy can give us that ability to act quickly, act boldly. There are also other kinds of science that really are not rewarded by typical grant review mechanisms. And philanthropy can give us the freedom to do large mission oriented kinds of science that we can't really do through federal funding.

Now, so this is sort of like your retirement portfolio. We want to have a diverse source of funding to have kind of the bread and butter science. We want to have high risk, high reward. We want to have things happening quickly and also those that are tried and true through review mechanisms.

So we really need an appropriate blend of federal funding, philanthropy, and even private sector funding to make really big headway in autoimmunity.

Host: What an exciting time, and what makes Penn Medicine the perfect place for the Colton Center? While you're telling us that, give us a little bit of a blueprint for what the future looks like for autoimmune research. What are we going to see that's exciting?

John Wherry, PhD: Yes, well, Penn Medicine is really an interesting place to sort of be the hub of this Colton Center and a larger Colton Consortium that I'll mention more about in a minute. Penn Medicine is the place where we led the way for cancer immunotherapy using CAR T cells. Where, you know, researchers at Penn learned how to redesign and harness the power of the immune system to generate incredibly precise, sophisticated cell therapy for cancer.

It's also where mRNA technologies for vaccines and other kinds of therapeutics were invented. And gene therapy, the first gene therapy, FDA-approved drug was developed here at Penn that also took advantage of our understanding of the immune system.

 The reason why Penn Medicine really sits in this unique position is partly because of these previous successes in CAR T cells for cancer immunotherapy, mRNA vaccines, and gene therapy, but also because of a really powerful culture at Penn that allows us to move these kinds of ideas nearly effortlessly from the research bench to the clinic and back. And that not only brings new therapies to patients  incredibly quickly but allows us to learn from those new therapies every step of the way and improve them iteratively along that path.

With that strength, we've been able to build a center for autoimmunity here at Penn, the Colton Center, and also make that Colton Center at Penn the central hub of a four-institution consortium that includes NYU, Yale, and Tel Aviv University in Israel, to actually leverage what we've done at Penn and bring this knowledge and bring this approach to multiple other partners around the country and around the world.

(Host): Dr. Wherry, thank you so much for joining us today. That was a great discussion. To learn more about the Colton Center, visit pennmedicine. org. And to refer your patient to Penn Medicine, please call our 24 7 provider only line at 877 937 PENN or you can submit your referral via our secure online referral form by visiting our website at pennmedicine.org slash refer your patient.

That concludes this episode from the specialists at Penn Medicine. I'm Melanie Cole. Thanks so much for joining us today.