Immunotherapy offers a different approach to cancer treatment
July 5, 2016
When the subject of cancer treatment comes up in casual conversation, chemotherapy and its debilitating effects are usually part of the discussion. But immunotherapy, while lesser known, has drawn greater attention thanks to its ability to completely eradicate certain forms of cancer -- melanoma and renal cancer -- even when the disease has reached the metastatic stage. Also known as biotherapy, it uses the body’s own cells to fight and defend against cancer in a direct, targeted way, as opposed to the all-encompassing approach employed by chemotherapy.
Dr. Theodore Logan, an associate professor of clinical medicine at the School of Medicine and a physician scientist at the IU Simon Cancer Center, is an immunotherapy expert. He specializes in interleukin-2, a type of cytokine. Discovered in the 1970s, cytokines are proteins that carry messages or signals between cells, such as when to trigger the body’s immune system. They're produced by certain T-cells -- the white blood cells that play a crucial role in defending the body against infections and cancers -- to help other T-cells attack targets, Logan explained.
Logan has been administering cytokine-based immunotherapy since the 1980s, when he was a fellow in oncology and internal medicine at the University of Pittsburgh. He says that despite its relatively low profile compared to chemotherapy, immunotherapy has been around longer -- a lot longer, in fact. In the 1890s, Dr. William Coley, a surgeon in New York, began injecting patients suffering from cancer with "bacterial products" that came to be known as "Coley's toxins." Coley had observed cancer shrinkage in some of his patients with bacterial infections, Logan explained.
"Coley found that a small number of patients responded to the injections," Logan said. "At the time, it was the only known systemic treatment for cancer. It didn't really pan out. But it did lead to further evaluation of bacterial products in cancer treatment."
Enough of Coley’s patients responded to the treatment that interest in immunotherapy continued to develop, albeit at a slower pace than that of chemotherapy. In the 1970s, Dr. Lloyd J. Old discovered a cytokine -- dubbed "tumor necrosis factor" -- that caused tumors in mice to blacken and die, which led to interest in other cytokines, Logan says. This cytokine was induced by bacterial products much like Coley used. "Around the same time, there was another cytokine discovered at the National Institutes of Health that was shown to grow T-cells; it was called interleukin-2," Logan said.
In a way, however, IL-2 treatment was, at least initially, a victim of its own success. Early trials involving IL-2 produced dramatic results -- remissions lasting months and years -- in some patients suffering from metastatic melanoma and renal cell cancer.
"There was a whole lot of skepticism early on about IL-2 because it was the only treatment that caused these very dramatic responses in a small number of patients that could last for years," Logan said. "Yet there were many side effects, and it was thought that only a small number of patients would be able to tolerate it."
And now there are other immunotherapies that also cause responses in cancer patients, like T-cell checkpoint antibodies, so it becomes very difficult to dismiss the field.
"This is a field that's taken 120, 130 years to mature. It's not necessarily a new treatment even though it's in vogue right now," Logan said.
Thanks in part to the presence of Logan, who has dozens of clinical trials to his name, the Simon Cancer Center has consistently been able to offer IL-2 -- marketed by drug company Prometheus under the brand name Proleukin -- to patients for many years. Only three other medical centers in the state -- two in Indianapolis and one in Goshen -- offer the treatment.
"There are some private-practice doctors that do it occasionally," said Logan. "It requires a lot of work to administer properly. It's not something that's easily set up in most hospitals."
Logan said he was attracted to the Simon Cancer Center precisely because, at the time, it did not have a strong immunotherapy program. "This was an opportunity," he said, adding that the cancer center was already a well-known facility with a very strong clinical program when he arrived in 1999.
In addition to IL-2, Logan is an expert in other immunotherapy treatments, including the drugs interferon, Yervoy, Opdivo and Keytruda, among others. He was involved in the development of many of today's immunotherapies.
One of his non-Interleukin patients, 61-year-old Terre Haute resident James Haley, praised Logan's dedication to knowing all there is to know about the field of immunotherapy and what treatment program is most likely to work for each individual under his care.
"When it comes to cancer, the treatment, the drugs that are out there or any of the studies that have been done, he's demonstrated an extreme amount of knowledge of what’s worked and what hasn't,” said Haley, who was diagnosed with melanoma in 2009. "The other thing, if I go off cancer to something else medically, maybe something that would fall under the expertise of my family doctor, [Logan would] be the first to say, 'I don't know.' He doesn’t claim to know it all. But when my life was on the line, and it was a few times, I was ecstatic to know he was there."
Logan, who hails from Maine, obtained his medical degree from the University of Vermont and has worked in the biochemistry field. He said his passion for science dates back to his high school days, when he became interested in science and in being able to do something useful with it.
That passion has not dimmed. It has led Logan to work toward firmly entrenching IL-2 immunotherapy as a hallmark area of treatment and research at the Simon Cancer Center.
"We've been able to teach a cohort of nurses and people on an ICU floor to become familiar with it," he said. "We have outpatient nurses who are familiar with the follow-up. We have trained people how to give this treatment and recognize the side effects of it -- when it's safe and when it isn't."
Logan's team approach has not gone unnoticed. "His staff is remarkable," Haley said. "They have an uncanny way of working closely with Dr. Logan and conveying information to the patients. If I have any questions, I can call or email, and within a couple of hours, I get a response back that includes Dr. Logan's direct input."
Cytokine-based immunotherapy's transition from the fringe to the mainstream has not deterred Logan from further inquiries in the field. The arduous treatment process, which can result in toxicities requiring lengthy hospital stays, means that IL-2 treatment has yet to be fully explored in other forms of cancer. It also remains to be seen why certain patients respond to the treatment while others, suffering from the same type of cancer, do not. A recent clinical trial focusing on renal cancer patients did not provide the predictive data sought by investigators, Logan said, but a similar trial involving melanoma patients is in the works.
"When this was developed, in the early 1980s, the best responses were seen in renal cancer and melanoma, and so that led to more study and, ultimately, FDA approval in those two diseases," he explained. "But it hasn't been extensively studied in other diseases -- it may or may not work.
"We need to continue to learn about the biology of what’s going on. We need to be able to understand what we're doing. We need to develop markers -- ways that we might determine whether a treatment is working or not working. There's a lot of work to be done."
Still, he said, the results so far speak for themselves. "About 5 percent to 6 percent of the patients who get treated have a complete shrinkage that can last for years. And this occurs when they’re not being treated regularly," Logan said. "There are patients alive 10 years later. Not many, but there are. And they're not getting treated; they're just being followed."
One of them is David Wood, 67, of Anderson, who was first diagnosed with malignant melanoma in 1983. In 2001, the cancer metastasized, which led him to Logan. Initially, Wood received another immunotherapy drug called interferon.
"Dr. Logan supervised that at the beginning," Wood recalls. "He concurred with my oncologist that it would be my best treatment plan at the time. I finished that treatment in April 2002 and went 16 months before the cancer recurred again in 2003. I had three recurrences then within three months. So Dr. Logan felt I was a candidate for interleukin."
Wood's melanoma had spread to both lungs, where his lymph nodes were rapidly deteriorating. He knew that only a modest percentage of cancer patients can tolerate interleukin, but "I was down to a last resort," he says. Wood agreed to undergo the 14-dose IL-2 treatment plan recommended and supervised by Logan. The process involved extended hospital stays and side effects such as the temporary loss of all feeling -- including the ability to feel pain -- in his legs, arms and feet, but he persevered. Today, some 12 years later, he's cancer-free.
"Dr. Logan managed my care with a great deal of expertise," Wood said. "I'm alive today because of him. I had the best care you could have."
Logan knows of a cancer patient treated by a colleague who has been cancer-free even longer than Wood -- 18 years -- thanks to IL-2. And Buffalo, N.Y.-based Roswell Park Cancer Institute, one of the busiest IL-2 clinics in the country, claims to have had patients survive for decades after IL-2 was used to treat their metastatic cancer.
"It's pretty amazing -- if people respond, they can be off treatment and living their life," said Logan. "There aren't many things that can do that, even today."