Research to remove exclusions on immunotherapy

In Clinical Trials by Barbara Jacoby

By: Michael Hardy

From: mdanderson.org

People used to ask Patrick Hwu, M.D., why he decided to devote his career to melanoma, a skin cancer with high mortality rates and limited treatment options.

“They would come up to me and say, ‘How can you treat advanced melanoma? Isn’t that depressing?’ And actually, it was — my clinic of advanced melanoma patients used to turn over every six months. They used to all pass away, except for a very few.”

That’s starting to change, thanks largely to immunotherapy research by Hwu and others that explores treatments designed to boost a patient’s immune system so it can better fight cancer. Since joining MD Anderson Cancer Center in 2004, Hwu’s clinical and research work have investigated ways to improve outcomes for patients with melanoma, as well as other cancers resistant to more traditional therapies.

“Thanks to immunotherapy, we’re having a lot of success now,” says Hwu, who heads the division of Cancer Medicine. “Many of our patients are doing well for a number of years.”

A double-edged treatment

Immunotherapy supercharges the body’s immune system, making it more effective at killing cancer cells. Unfortunately, it also makes the immune system more likely to attack healthy cells. Because of this, people with autoimmune disorders such as arthritis, psoriasis, colitis, lupus, celiac disease, multiple sclerosis and many other diseases that cause the body’s immune system to attack itself were barred from the clinical trials of the first immunotherapy drugs. Autoimmune diseases are extremely common — an estimated one in every five people has one — which means that a significant number of patients are excluded, for now, from some of the most promising new cancer treatments.

“We have patients who come to us who have both cancer and arthritis,” Hwu says. “So, then what do we do?”

One such patient is Bob Wilkes, who already had arthritis and psoriasis before being diagnosed with stage 4 melanoma. “When I learned I had cancer, my wife and I knew we faced an uphill battle, with surgery and chemotherapy in our future,” says Wilkes.

But when the couple inquired about immunotherapy, they learned Wilkes wasn’t eligible because he had autoimmune issues.

“Immediately, my wife and I asked ‘Why not?’” Wilkes recalls. “Dr. Hwu’s word-class research team responded to our question the same way and asked, “Why not indeed?’”

Wilkes, who owns a successful cabinet-building company headquartered in South Carolina, donated $1 million to launch a research program that will help Hwu and his team contribute toward discovering new treatments for patients with cancer and autoimmune diseases.

“We want to find a way to cure not only cancer, but also autoimmune diseases,” Wilkes says. “We want to fight back.”

To extend the benefits of immunotherapy to people suffering from arthritis and other autoimmune disorders, Hwu and his research team, led by Roza Nurieva, Ph.D., associate professor of Immunology, and Weiyi Peng, M.D., Ph.D., assistant professor of Melanoma Medical Oncology, have been inducing arthritis and cancer in mice, then testing various treatments on them. The hope is to come up with a combination of drugs that will kill the cancer without exacerbating the arthritis. “You have these dueling effects,” Hwu explains. “You have one drug that stimulates the immune response to kill the cancer, and another drug that dampens the immune response to improve arthritis. Will they cancel each other out? Or can we distinguish the two pathways?”

A potential target

The team’s research has led them to focus on interleukin-17, or IL-17, a critical molecule that facilitates communication between immune cells. Many immunotherapy treatments seek to boost production of IL-17 in order to better kill cancer cells. But according to Hwu’s research, such treatments may do more harm than good, increasing autoimmunity without substantially improving the system’s cancer-fighting abilities. If their hypothesis is borne out, cancer patients with autoimmune disorders could potentially take an IL-17 blocker to counteract the effects of their immunotherapy regimen.

Because immunotherapy is so powerful, even cancer patients without a diagnosed autoimmune disorder sometimes develop one during the course of treatment.

“We want to stimulate the cells that recognize the cancer without stimulating the cells that cause autoimmunity,” Hwu says. “We would be dead without our immune system, but our immune system can also wreak havoc.”

Hwu says that because immunotherapy treatments are so new — many have only recently gained approval from the Food and Drug Administration — researchers are still figuring out the best ways to use them.

“The immunotherapy revolution has just started in the past five years,” he says. “We’ve been working on it for decades, but the flurry of FDA approvals has just come in the past few years.”

One of the side effects of Hwu’s research may be the development of better treatments for autoimmune diseases in patients without cancer.

Hwu compares the immune system to a squadron of tanks circulating in our bodies, guarding us from foreign invaders:

“You want the tanks around, but the problem is if these tanks accidentally have an issue and start firing away at other parts of your body. That’s called autoimmunity. The goal of all these studies is to get the tanks to kill the cancer, but not kill our normal organs. Can we give a therapy that decreases the collateral damage? That’s our whole goal as immunologists.”