Share ThisIt’s safe to say that the coronavirus has strengthened a general consensus that viruses are our enemy. However, our collective fear of viruses goes beyond COVID-19. From Human Immunodeficiency Virus (HIV) to Ebola, influenza, and many others, the damage caused by viral agents is vast and far-reaching.
But is devastation the only story when it comes to viruses? Renowned cancer researcher and surgeon, David L. Bartlett, MD, offers another perspective. For the last 25 years, he has been researching ways that viruses can be used to fight and win against another enemy: cancer.
Now chair of the Allegheny Health Network (AHN) Cancer Institute, Dr. Bartlett came to AHN from the University of Pittsburgh Medical Center, where he held various leadership roles. He joins AHN in the midst of significant growth, including the opening of a $78 million Cancer Institute Academic Center at Allegheny General Hospital, which will serve as a hub for cancer research like his.
In a time of social distancing, we connected via telephone to discuss how viral cancer therapy is proving that the enemy of your enemy can sometimes be your friend.
Dr. David L. Bartlett, chair, AHN Cancer Institute
Emily Laubham (EL): Before we jump into your research, let’s talk about your work with patients. What kinds of cancer patients do you typically see, and what ways are you able to help them?
Dr. David L. Bartlett (DB): My specialty is complex abdominal tumors and any kind of cancer that involves the abdominal cavity — stomach cancer, liver cancer, colon cancer, and sarcomas (soft tissue tumors). I tend to treat many recurrent and metastatic, secondary cancers. This means we take a lot of patients who have lost hope and feel like they’ve run out of options.
We perform specialized procedures — hyperthermic intraperitoneal chemoperfusion (HIPEC) — to remove tumors and then treat the abdominal cavity with chemotherapy that is recirculating through a heat exchanger. Essentially, we’re bathing the insides in chemotherapy and heating the abdomen to try and prevent tumors from coming back. We can help patients, very dramatically sometimes, and give them real hope with these procedures.
EL: You see patients, perform surgery, do advanced research, and now also serve as institute chair. Can you talk about the connection between these different roles?
DB: They all come together in that, when we’re treating cancer patients, we’re always trying to come up with the best possible approaches. In my practice, because I’m dealing with metastatic and recurrent cancers, surgery is often not curative. That motivates the research, which is looking into developing better therapies that can change patients’ lives when other therapies haven’t helped.
Having the research lab and models for the exact type of cancer patients I treat allows me to improve the therapy as well. The patients coming to me are good candidates for the treatments we test. Both HIPEC and the viral treatments are options that people would turn to when they run out of standard options. That knowledge drives me.
I started in research at the National Cancer Institute. Then I came to Pittsburgh and took on clinical and administrative roles. As chair at the AHN Cancer Institute, I’m now hoping to inspire others to build similarly research-driven programs.
EL: You’ve been conducting research into how viruses can be used to fight cancer. How does this work?
DB: It always intrigued me to think, what if you took a virus — which can replicate and divide and take over the body, like with COVID-19 — but then “trained” it, so to speak? What if you mutate it so that it would only replicate and divide and spread through cancer cells, but not through normal tissue? So, that became my interest — to train or mutate replicating viruses to selectively damage, injure, and kill cancer.
There are different ways that people have gone about this, but my team was one of the first to do it using a poxvirus, Vaccinia Virus, which is a cousin of smallpox. It’s one of the most aggressive viruses known to man that we’ve been able to mutate so that it selectively infects and divides in cancer cells only.
We tested a number of different viruses, but this was our favorite. It was the most efficient and effective, so that’s what we’ve focused on.
EL: Would viral therapy be administered to patients as perfusion, like HIPEC?
DB: Yes, our interest is in filling up the abdomen with the live virus so it directly infects the cancer cells. Also, this way we don’t have to worry about it getting cleared in the bloodstream on its way to the cancer.
Since we created the tumor selective virus, we’ve also been playing around with different payloads to induce an immune response in the body. The poxvirus can express genes that lead to an immune response, so even if the cancer cells aren’t infected by the virus, the immune system can be encouraged to attack the cancer. In that sense, it is also a type of viral immunotherapy.
EL: Who would be a good candidate for the kind of treatment explored in your research?
DB: Patients with peritoneal spread of cancer, which would include colon cancer, ovarian cancer, mesothelioma, stomach or gastric cancers, and abdominal sarcomas. So, basically any tumor that spreads in the abdominal cavity would be able to respond to this. The virus seems to be agnostic to tissue type — in other words, it seems to work just as well in colon cancer as it does for sarcoma or lung cancer.
EL: How far along is your research? Is it still in clinical studies?
DB: I’ve been doing this research for 25 years. We have gone through two clinical trials with this particular virus, and others have used the technology that we developed. It’s been tested in humans, but it’s still not at the point where we can take it to the FDA for final approval. We’re still continuing to work on ways to improve the virus.
EL: What barriers still exist to making this a widely available treatment?
DB: There’s a struggle with these viruses to have them kill enough cancer before the body’s immune system takes care of the virus like it’s designed to do. That’s been the primary struggle to make this more clinically relevant and able to be used to treat patients.
EL: Are there similar virus-based approaches that have been FDA-approved?
DB: There is a virus — a herpes virus — that was approved to treat melanoma. It is the same concept as what I’m talking about with our research, but there are ways we think we can improve upon it with the virus we use and the additional payloads. What we’re finding is that because of the patient’s immune system, we can deliver the virus into either the tumor or into the abdominal cavity as a perfusion like HIPEC. And so we’re looking at regional and local delivery as a way to induce an immune response that clears the cancer from the patient.
EL: Are there any studies or branches of your research that you’d like to discuss?
DB: Our latest research uses the virus to infect tumor cells, then we collect the T-cells — the immune cells — that infiltrate the tumor in response to the virus. We expand those cells outside of the body and then give them back to the patient. What we’re finding is that those T-cells react against and kill the cancer.
Basically, this is going one step further in our research and saying, “Well, if we can’t get the virus to infect all of the cancer cells, what if we just get it to infect one tumor nodule and then harvest that nodule?” From there we take out the immune cells, expand them, give them back, and let them treat the body. This has been effective; we have a couple publications coming out on the process.
Adoptive cell therapy (CAR T Cell) is a form of this, too. It is utilizing the virus to optimize tumor-infiltrating lymphocyte therapy (TIL), which we know to be effective, but only if the lymphocytes — white blood cells and one of the body’s primary immune cells — are right. By using the virus in what we call pre-TIL approach, the lymphocytes can be harvested and activated against the tumor.
One of the exciting new findings is a way to tether immune protein cytokines and chemokines to the cell that is infected with the virus. If a virus produces a protein that is secreted and goes throughout the body, it can be very toxic, but with these tethered proteins, the virus only affects cancer cells. The proteins are bound to the cancer cells, and it creates a better, safer vaccine or vaccination strategy. Now, those kinds of tethered cytokines can be used, not just with viral therapy, but with other forms of gene and cellular therapy like CAR T Cell.
EL: How do you see your research shaping the future of the AHN Cancer Institute?
DB: By bringing this research here, it introduces a new field they haven’t been involved in historically, and so all the tech associated with creating viral mutations, working with the virus, and all the potential applications will help other researchers here.
I think the whole model of translational research, and specifically performing research on the disease you treat, will hopefully be a model that we can replicate in other programs and other disease sites. That would allow us to recruit scientists that can come in and help build something new, expanding the culture here toward more research and discovery.
Dr. David Bartlett is chair of the AHN Cancer Institute. An internationally recognized cancer surgeon, he is a pioneer in abdominal cancer treatment and a dedicated, prolific researcher. He is past president of the Society of Surgical Oncology.
He served as a senior investigator in the surgery division of the Center for Cancer Research at the National Cancer Institute, where he developed innovative surgical techniques to treat patients with abdominal and liver cancers and performed cutting-edge laboratory research in viral-based immune therapies.
Dr. Bartlett received his medical degree from the University of Texas Medical School at Houston and completed his surgical residency at the Hospital of the University of Pennsylvania in Philadelphia, Pennsylvania.
He continued his training with a Fellowship in surgical oncology at Memorial Sloan Kettering Cancer Center in New York City. He completed research fellowships at M.D. Anderson Hospital in Houston, Texas, and the Hospital of the University of Pennsylvania.
Board-certified by the American Board of Surgeons, Dr. Bartlett holds membership in several professional surgical and oncology societies. He received many academic honors during his career and has been chosen as one of Pittsburgh’s Best Doctors every year since 2006.
He has published over 300 research papers in medical journals and has contributed chapters to more than 40 publications. In addition, he lectures widely at national and international meetings and conferences.
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