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The Role of Immunotherapy and Oncolytic Viruses in the Future of Cancer Treatment

Greg Kennelty
Published Online:3:43 PM, Tue August 23, 2016

Howard Kaufman, MD
Immunotherapy may not phase out surgery and chemotherapy as standards of care in cancer, but oncolytic viruses may usher in a new age of treatment.

In an interview with Targeted Oncology at the Society for Immunotherapy of Cancer (SITC) 101 program, Howard Kaufman, MD, associate director, Rutgers Cancer Institute of New Jersey, and president of SITC, discussed how far immunotherapy has come as a treatment, where the field is headed in the future, and how oncolytic viruses could play a major role as treatment in the future.

TARGETED ONCOLOGY: In the past 10 or 12 years, what kind of advancements have we made in the field of immunotherapy?

Kaufman: Immunotherapy has really developed, especially over the last 5 years, and I think in addition to having a number of new approaches—including the T-cell checkpoint inhibitors, oncolytic viruses, and a lot of work going on with combination therapies and adopted T-cell therapy—one of the most important points is that it works in many different types of cancers. We used to think of immunotherapy as only something for some patients with melanoma, maybe some patients with renal cell carcinoma, but we now know that it may work in almost every type of cancer. Different drugs may be needed and different combinations may be needed, but I think the field is very exciting right now. We need to get people in it, we need to study it, and we need to do trials faster to really understand the full potential of this treatment.

TARGETED ONCOLOGY: As immunotherapy becomes more popular, where do traditional therapies, such as surgery and chemotherapy, place as treatments?

Kaufman: The standard therapies like surgery and chemotherapy are going to continue to be important and play a role. One of the interesting developments is that we're now looking at some of the standard therapies and understanding their impact on the immune system. This is already leading to some early preliminary data that suggest that immunotherapy could be combined with some of these other approaches. So I think surgery will be the mainstay, and it will be important for making diagnoses and for really providing benefits to patients. The role of chemotherapy and targeted therapy, and even radiation therapy, with the immunotherapy, is a particularly exciting area.

We know with chemotherapy, one of the problems is that even when it works really well, it can't get every single cell. Envision the immune system coming in and going after those kinds of stray cells—it's a particularly interesting concept that I think we're surprised about and historically, we've considered that chemotherapy might suppress an immune response. It might in certain situations, but in other scenarios, it can actually enhance an immune response.

TARGETED ONCOLOGY: Where are we with using different types of viruses to fight cancer?

Kaufman: I think oncolytic viruses are particularly exciting, because this is my area of research. The first oncolytic virus was approved by the FDA last year to fight melanoma. The viruses are now being studied in many different types of cancer, and I think the success of the T-VEC oncolytic virus is really leading to studies with other oncolytic viruses, and in a wide range of different cancers. We are already learning that some cancers may be more susceptible to certain viruses, and we're also getting the first data on combinations of oncolytic viruses with other immunotherapy agents.

Some recent data that was published really suggest some very strong effects with this. I think the oncolytic viruses also offer an interesting advantage so far in the safety profile, in that they have been very tolerable. Most of the side effects that occur with these are low-grade constitutional symptoms and local injection site reactions, and most of these are very short-lived and disappear within a few days.

TARGETED ONCOLOGY: In what kind of setting are these oncolytic viruses being used right now?

Kaufman: The oncolytic viruses are only approved to treat melanoma right now, but the studies that are ongoing are ones where the tumor is accessible. One of the issues with oncolytic viruses is that the virus has to get into the tumor. Tumors that are in or under the skin are particularly attractive targets for oncolytic viruses. So things like chest wall recurrences from breast cancer, sarcomas, particularly in the extremities, head and neck cancers, as well as some of the non-melanoma skin cancers, are all kind of high priorities.

Having said that, we now can use interventional radiology technology to get into almost any tumor. So some studies have started where we're trying to get into the liver using a CT-guided injection of oncolytic viruses. It'll be interesting to see if we can't target more of the visceral tumors, and some viruses are amenable to systemic administration. It can be given through IV, though some of them will be wiped out by circulating antibodies, but some may survive that and can preferentially infect tumors.

The field is going to require more research, but again, it's an exciting time in this area.

TARGETED ONCOLOGY: Were there many side effects or toxicities that were seen from these viruses?

Kaufman: We saw low-grade fever, some fatigue, some pain at the site of the injection, but again, these were generally low-grade and fairly easy to manage. Overall, I think it was well tolerated. We had no deaths in the oncolytic virus studies that were done, so it seems to be a relatively safe approach.

TARGETED ONCOLOGY: Where do you see this field going?

Kaufman: The field is going to be booming. I think we're going to be seeing every cancer being impacted by immunotherapy, and we're going to understand a lot about what combinations to put together. My personal view of the future is we're going to have what I would call precision immunology. Just like today, we can look at the genetics of a tumor and understand what mutations we might be able to target in the patient. We're going to understand what portion of the immune system is not working in an individual patient, and we will be able to correct that deficit and restore the immune surveillance function that I think we're all born with.

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