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A ‘living drug’ that beats cancer | ASU KEDtalk

Could unleashing the body’s immune system cure cancer? Karen Anderson reveals how a scientific breakthrough that empowers the body’s own cancer-killing T cells offers new hope.

You may not know this, but you may be a cancer survivor. What do I mean by that? It turns out, the very act of living, of growing, is associated with DNA replication. And while DNA can replicate with high fidelity, sometimes there are errors or mutations in our genome. Now usually, that happens in safe spaces in our genomes, where it doesn’t have an impact. But sometimes that happens in the very genes that drive tumor growth and development. When that happens, cancer can develop. 

So why don’t we have cancer? Our T-cells that are trained to distinguish viruses and bacteria are circulating throughout our system. And they are trained to distinguish cell from non-cell. This is a healthy cell. This is an infected cell. 
And it turns out, T-cells can also distinguish cancer cells from healthy cells. To a T-cell, these cancer cells look like a virus. As a result, our T-cells may be killing off tumor cells again and again. 

But cancer evolves to evade the immune response. It can become invisible, like the invisibility cloak of Harry Potter and can sit right next to a T-cell without being seen. In the spring of 2010, my field of cancer immunology all changed. That was the first time in a large-scale clinical study that it was shown that immune therapies that just activate T-cells can impact the lives of patients with malignant melanoma. 

Now, cancer immunotherapy is now commonly used across many different cancer types. So what we found is that the cancer cells that are most mutated, that are most altered, that are most aggressive are also the ones that are most visible to T-cells. So imagine these T-cells chasing down the tumor cells and killing them. 

So now, we can sequence those tumors. We can identify the changes in the cancer cells. We can develop vaccines and T-cell immune therapies to try to target the very changes that are happening within those tumors. From leukemias to breast cancers, we’re just harnessing what was there all along. 

So one of the challenges is that every cancer is different. My lung cancer may be different than your lung cancer. My immune system may react differently than your immune system and differently than my twin. So we have to be very precise in how we develop these immune therapies. 

My laboratory develops ways to look at the breadth and the specificity of the immune response to cancer. How can we target it? How can we use it? How can we deliver it? Can we even do without chemotherapy? Is this the year it all changes again?

A Living Drug That Beats Cancer | ASU KEDtalk

Tricoles: Welcome to ASU KEDtalks, the podcast. I’m your host Robin Tricoles and I’m here with Karen Anderson, a researcher at ASU’s Biodesign Institute and a clinician based at the Mayo Clinic in Scottsdale, Arizona. When Anderson is not in the clinic treating patients with breast cancer, she’s in her lab studying immunotherapy, a new way of treating various forms of cancer. Hi Karen. Thanks for being here.

Anderson: Good morning, Robin.

Tricoles: Would you briefly explain what immunotherapy is?

Anderson: Well, the goal of immune therapy is to harness the immune system to target cancer. And there are many ways you can do that. We know that the immune system is already there. It’s already trying to track and to target cancer naturally, in fact. But the cancer evolves and it grows and it, it develops ways to evade the immune system. And so immune therapy is about activating T-cells, about giving antibodies, about trying to create a strong immune system so that the cancer can be killed. And one of the advantages of that is that the immune system can go anywhere, all right? It can go anywhere in the body and try to kill off those, those rogue cancer cells that might have traveled.

Tricoles: When we talked previously, you had mentioned that, immunotherapy appears to have been around at the turn of the 20th century and was even mentioned in the New York Times back then. Can you tell me a little bit more about that?

Anderson: Yeah, the history is fascinating. It started, I would say with Coley’s toxins, which was essentially like a bacterial lysate, like an extract that was delivered into tumors, and what it turned out, what it was really doing was trying to activate a lot of the innate immune response in and around the tumors. And so this had gotten some, some news and some press back then and there were some isolated cases of responses and that led to that plus the, the burgeoning field of, of immunology really led to a lot of work over a period of really a century trying to identify how to harness it, how to target it, how to get it to work. But, but it was really not until the last five, really, I would say 15 years that we have been able to harness it specifically and directly to really show a benefit consistently for a number of patients.

Tricoles: Why has it been the last 15 years, do you know?

Anderson: Well, it’s about understanding the individual molecules that regulate the immune system. So one of the amazing things about your immune is that it’s, it’s balanced. It, it always is, is balancing between fighting an infection and then recovering from that without causing auto-immunity, without being too activated. Because when that happens, you get really sick. And so there’s all these, these redundant pathways, these redundant molecules, that help govern it. It’s, I liken it to having your foot on the gas and the brake at the same time on a car. And so that, that way, if you just manipulate one of them a little bit, it, it either stops you or pushes you forward very, very quickly.

Tricoles: When we talked before, you’d also mentioned that there was a breakthrough in immunotherapy that came in 2010, and it was for metastic melanoma. If I’m remembering correctly. What did you think about that breakthrough, and why melanoma as opposed to another type of cancer?

Anderson: Yeah, the history is interesting, but there were many, many trials over decades of people trying to show can we drive T-cell responses, can we drive immune therapies to cancer? And it was very clear in all the preclinical models that, that it was feasible. But when it came to actually treating patients and treating tumors, it was really difficult. And one of the keys for that particular study, we had hints earlier on and in earlier clinical trials that that was going to be feasible. But melanoma in particular is a very immunogenic tumor. We’ve known that for a long time. It’s, it’s relatively resistant to chemotherapies and, but it’s very sensitive to the immune system. So in fact, one of the therapies that we’d already been using for melanoma was a cytokine, basically an immune therapy anyway.

Anderson: But this was the first time that just activating the T cells could then target the melanoma. And it’s the same pathway our immune system uses anyway to shut itself off. And what they do is they just blocked it and then activated all those T cells. And it turns out that for some patients with the melanoma that had a really important and most importantly, a durable effect. So it didn’t just happen and work briefly, but it, but it worked for a long time and it wasn’t as if the cancer was, was gone away. A lot of times it’s just, it’s putting it into, into what we call homeostasis, but, but into a balance. It’s sort of like the immune system sees it, the cancer’s there, but neither of them are winning. You are at a truce, but a truce means the cancer is not growing and it is a win.

Tricoles: With immunotherapy. It seems that the focus on cancer treatment has turned away from the tumor. Are tumor bank still important for research, and if so, why?

Anderson: Oh my goodness, they’re so important. Everybody’s cancer is different. Everybody’s immune system is different. But the, not only is everybody’s cancer different, but there’s a lot of heterogeneity within those tumors. So one part of the cancer or one metastasis from the cancer may be genetically different and behave differently than another. Oncologists have known this for a long time and patients have known this. You might be under a therapy for a while and most everything is responding, but one spot might not be responding. And because it’s acquired different mutations, it’s acquired resistance. So tumor banks help us dissect all that out and help us figure that out. Otherwise we’re, we’re using model systems that are much more homogeneous and, to understand, to me that’s one of the advantages of the immune system is that it’s a diverse system to begin with. It has incredible diversity because it doesn’t know what’s coming at it, right? It might be a virus, it might be a bacteria might be a fungus, I mean it has to have this incredible defense system. You have no idea what’s coming at it. So it has to adapt to that. And the same is true for trying to fight cancer, right? Because cancer may have one mutation or different mutations or different genetic changes. It could be a lung cancer or a melanoma or a bladder cancer. I mean any of those. And so that’s where the diversity is, is a real strength.

Tricoles: Now, what is your dream when it comes to treating patients with cancer?

Anderson: I think that in the near future, I think we will find ways to vaccinate people and treat people with immune therapy after their diagnosis. And with the goal to prevent recurrence. Could we actually do without chemotherapy? Could we do without surgery? Can we do without radiation? You know, these are all unanswered questions, but I think we’re just really scratching the surface of what these treatments can do and how to tailor them for different types of cancers, because there are many different molecules involved in the process. So there are a number of different drug targets that are coming down the pike. But I think we have this opportunity, maybe it’s vaccines and targeted immune therapy, maybe it’s adoptive T cells and car-T therapies. And it may be different for different types of treatment, but if we can do this to reduce recurrence rates, we’re going to have a real impact on the, on the lives of, of cancer survivors.

Tricoles: So can I ask, what made you go into medicine and in particular oncology?

Anderson: Wow, that’s a great question. I have always been interested in science. I mean from the time I was in middle school and high school, I am, both of my parents are chemists and we sat around the table talking math and science. I mean, this was part of our growing up and my, my brothers are all engineers and mathematicians and computer scientists, you know, that’s what we do. We have very little artistic talent amongst us. But, when I, you know, I went to college at the University of Virginia and I volunteered in a research laboratory there and that really made a difference for me. It was back when we were just starting DNA sequencing and PCR didn’t exist and, you know, simple things like that, that we weren’t doing yet. And learning and understanding that every day was going to be different when I came in. And, to me, just being able to do that as part of my research and also being able to bring that to patient care was, I figured that would be a great way to spend my life.

Tricoles: In that vein, if you weren’t a physician and a researcher, what would you think you’d be doing instead?

Anderson: I’d probably be a large animal veterinarian, but, if not that maybe I’d run a bakery somewhere in the world somewhere. Yes.

Tricoles: Do you bake?

Anderson: Not well. [laughs] I’m not sure anyone would come, but yes.

Tricoles: If you’re interested in more from Karen Anderson, watch the ASU KEDtalks video at research.asu.edu/kedtalks. Subscribe to our podcast through your favorite podcast directory and find us on Facebook and Twitter @ASUresearch.

Karen Anderson is a researcher in the Biodesign Institute, which is partially supported by Arizona’s Technology and Research Initiative Fund. TRIF investment has enabled hands-on training for tens of thousands of students across Arizona’s universities, thousands of scientific discoveries and patented technologies, and hundreds of new start-up companies. Publicly supported through voter approval, TRIF is an essential resource for growing Arizona’s economy and providing opportunities for Arizona residents to work, learn and thrive.