New developments in immunotherapy treatments are changing the outlook for many patients with kidney cancer, but there is still much to be learned, researchers say.
Recent developments in immunotherapy have shown great promise for treatment of kidney cancer—especially renal cell carcinoma, which is the most common type of kidney cancer. The new wave of treatment for kidney cancer has been in the development of checkpoint antibody therapies, said Eric Jonasch, M.D., an oncologist, researcher, and professor specializing in kidney cancer at The University of Texas MD Anderson Cancer Center in Houston.
These new immunotherapy drugs are helping kidney cancer patients live longer, and in some cases are leading to a complete remission of the disease, said Pavlos Msaouel, M.D., a doctor and researcher also specializing in kidney cancer at The University of Texas MD Anderson Cancer Center.
Both Jonasch and Msaouel doctors spoke with HealthCentral by phone.
Many of these new immunotherapy developments were discovered through the research of Jim Allison, Ph.D., chairman of immunology and executive director of the immunotherapy platform at The University of Texas MD Anderson Cancer Center. Allison won the Nobel Prize in 2018 for his work in this field.
“Dr. Allison’s research in understanding how our bodies turn down the immune response, and how we can block that downturn in the immune response, has resulted in extremely effective new therapies that allow the immune system to recognize and kill cancer cells,” Jonasch said.
Ground-breaking Developments in Immunotherapies
Recent breakthroughs in kidney cancer treatments include the immunotherapy drugs ipilimumab and nivolumab. In 2018, the FDA approved using these drugs in combination as checkpoint inhibitors to treat kidney cancer. These drugs work by taking “the brakes off” of the immune system.
“This therapy has been a breakthrough,” Msaouel said. “The reason why it’s exciting is, based on trial data, this is the first therapy to produce responses in 42 percent of patients. And about 9 percent of patients will have a complete response; the cancer will be gone.”
How Do Checkpoint Inhibitors Work?
Our immune system works by circulating T-cells throughout our body, which identify and destroy cancer cells, while leaving healthy cells alone, Jonasch explained. The immune system does this through checkpoint proteins found on both T-cells and on healthy cells. However, some cancer cells also have checkpoint proteins, which they can use to shut down T-cells and avoid being detected.
T-cells have a checkpoint protein known as PD-1, which acts as an “off switch” so it won’t attack healthy cells. However, if a T-cell comes into contact with a kidney cancer cell that expresses a PD-1L protein, it will bind to T-cell’s PD-1 protein, effectively turning the T-cell off and preventing it from destroying the cancer cell.
Checkpoint inhibitor drugs work by blocking these proteins from binding, thus boosting the immune system’s ability to recognize and destroy cancer cells.
“What these therapies do is they act like a safety cap over the PD-1 on T-cell, so when the T-cell comes close to a cancer cell, the cancer cell can’t push the PD-1 button to shut off the T-cell,” Jonasch said.
Kidney cancer is among a handful cancers where checkpoint inhibitor drugs have been successful. Researchers are still trying to determine why some cancers respond better than others.
What New Research Is Taking Place for Immunotherapies in Kidney Cancer?
The new frontier in kidney cancer research is examining the potential use of other checkpoints in the immune system. “The goal is to understand if any of these other checkpoints are equally important and if blocking any of those can enhance the immune response,” Jonasch said.
Also, while T-cells are considered the main drivers for immune responses, researchers are also looking at the role and importance of other cells in the immune system, such as suppressor cells, and how these cells may also affect the immune system response, Jonasch said.
Another area of study is looking at the use of immunotherapies for patients who have earlier-stage kidney cancer, Msaouel said. Up until now, most clinical trials focused on patients with metastatic or end-stage cancer.
Msaouel is currently working on a clinical trial on the use of immunotherapies for early-stage kidney cancer, and if using these therapies before surgery (i.e., as neoadjuvants), can improve outcomes. Other trials are investigating how effective these therapies are after surgery (i.e., as adjuvants).
Limitations of Immunotherapy to Treat Kidney Cancer
The success of immunotherapies in treating kidney cancer can depend on the type of kidney cancer you have, Msaouel explained. Immunotherapies, including checkpoint inhibitors, have been shown to be effective in treating clear cell renal cell carcinoma, the most common type of renal cell carcinoma. However, these treatments aren’t always as effective in less common types of cancers. Researchers are now starting to look more closely at the effectiveness of immunotherapies in treating other types of kidney cancer. Msaouel himself is leading a clinical trial looking at the use of immunotherapies for renal medullary carcinoma, a rare and difficult-to-treat type of kidney cancer.
Dealing With Challenging Side Effects
While immunotherapies present a major step forward in kidney cancer treatment, there are challenges to this treatment. Doctors are examining how to best manage potentially serious side effects caused by immunotherapy drugs.
Unlike chemotherapy, where side effects are well known and often occur shortly after the treatment is administered, side effects with immunotherapies can vary widely from person to person, Msaouel said.
Immunotherapies can create toxicities within in patients that can range from mild to potentially dangerous and life-threatening. These side effects are caused when the immunotherapy begins targeting healthy cells in a patient’s body, rather than “bad actor” cancer cells.
For instance, if an immunotherapy begins targeting healthy cells in digestive system, it may cause diarrhea. If healthy skin cells are targeted, it can cause a rash, Msaouel said. But it’s hard to say where or when, or even if a person will develop these side effects.
Once the treatment starts targeting healthy cells, this indicates that the immune system has become overactive, Msaouel said. The treatment must then be discontinued to limit the immune system from attacking healthy parts of the body.
Kidney Cancer Has Long Been on the Forefront of Immunotherapy Treatment
Immunotherapies have come a long way since they were first developed more than three decades ago. And kidney cancer has showed promise in being treated with immunotherapy since the early development of these drugs, Msaouel explained.
Starting in the early 1990s, patients with metastatic kidney cancer were treated with interleukin-2, a first-wave immunotherapy drug. While the treatment resulted in about 7 percent of patients going into remission, it also caused severe toxicity and dangerous side effects in many patients.
“Interleukin-2 was tough, very tough on patients,” he said. “But it did show that immunotherapy as an approach could produce curable responses. That’s why it’s so exciting that we have new agents that can harness the immune system in new ways to treat kidney cancer.”
The medical world had to wait several decades for the next wave of immunotherapy drugs, but more developments are on the horizon.
“I think we are just beginning to learn how to best to harness and use these new approaches,” Msaouel said.
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