Immunotherapy causes paradigm shift in cancer treatment

Zihai Li, M.D., Ph.D., is fascinated.

The leader of the Cancer Immunology Program at the MUSC Hollings Cancer Center is sitting across from someone rare: a person who understands immunotherapy as both doctor and patient.

“It’s exciting,” Li says, leaning forward as he and Nicole Dominiak, M.D., discuss the treatment she’s undergone for melanoma.

“I feel very blessed,” Dominiak says.

Li feels blessed, too, to be working at a time when cancer treatment is undergoing what he calls a paradigm shift. Immunotherapy, the use of drugs to take the brakes off the immune system to help it fight cancer, is a key component of that. 

“I don’t think there’s anything that compares to this moment,” Li says.

Neither does Juan Varela, M.D., Ph.D., a faculty member in Hematology and Oncology who works with the MUSC Hollings Cancer Center’s Immunology Program. He says doctors are finally seeing the results of decades of basic cancer immunology research. 

“The recent clinical trial results really justify and solidify our belief that our immune systems are capable of recognizing, targeting and destroying tumors,” Varela says.

While immunotherapy only works in about 20 percent of all cases – doctors are trying to pinpoint the various reasons for that – when it does work, the results can be remarkable.

Examples abound. Last month, researchers testing the immunotherapy drug pembrolizumab on lung cancer patients found it worked so well that they stopped the study and gave it to everybody in the trial. It’s the same drug that former President Jimmy Carter said beat back his stage four melanoma.

And not long before that, two other studies made international news after finding that immunotherapy drugs were working against some cases of head and neck cancer, along with the often deadly skin cancer Merkel cell carcinoma, which is notoriously hard to treat. It marked the first time that immunotherapy had been successfully tested on cancers that can be triggered by viruses, which cause an estimated fifth of all cancers.

Immunologist John Wrangle, M.D., says for some patients at MUSC Hollings Cancer Center, immunotherapy is now a critical part of treatment. “It’s become standard of care. Essentially all of my patients will be treated with immunotherapy at some point in the course of their disease. This is patients who have unresectable, incurable disease. Immunotherapy is essential to lung cancer treatment these days.”

Li says immunotherapy works by outsmarting tumor cells. “We have learned that one of the key hallmarks of cancer is its ability to turn off the immune response. Scientists have figured out multiple ways to turn the immunity against cancer back on. Remarkable results, including cure, have been seen with immunotherapy.”

MUSC Hollings Cancer Center, a National Cancer Institute-designated cancer center, does more immunotherapy trials and treatments than any other institution in the state. It has 24 investigators actively working on immunotherapy, Li said. Some are currently involved in a trial testing whether a two-drug combination works against non-small cell lung cancer, the most common type.

And last year, in another important development, MUSC researchers Mark Rubinstein, Ph.D. and Chrystal Paulos, Ph.D. announced that they and their colleagues had found that using engineered cells in immunotherapy, a process called adoptive cellular therapy, showed great promise. Engineered T cells were used in the lab to recognize and kill melanoma tumor cells.

MUSC researchers have also tested immunotherapy drugs on lung, kidney, melanoma, cervical, sarcoma, head, neck and pancreatic tumors. 

But Li said there are a lot of things to keep in mind when it comes to immunotherapy. First, he said, immunotherapy is not magic that melts away cancer. “We don’t want to create too much hype. It’s a new way of treating cancer, and some people will respond when all other options are out. Could this be you? We’ll try.”

Second, cancer progresses differently in different people, so it’s important to try multiple pathways to fight it. That includes combining older treatments such as chemotherapy and radiation with immunotherapy.

Third, immunotherapy has great potential for people newly diagnosed with cancer. “We’ve been treating patients who are out of options,” Li said. “We need to learn more about what happens if you bring in immunotherapy up front, before chemo or surgery.” 

Types of immunotherapy include, according to the National Cancer Institute:

• Monoclonal antibodies (aka targeted therapy), which are drugs that bind to or mark cancer cells so the immune system can find them more easily
• Cytokines, which are proteins made by the body’s cells that help the immune system fight cancer
• Vaccines, which boost the immune system’s response to cancer cells
• Bacillus Calmette-Guerin, which is a bacteria used to treat bladder cancer

All are being used at MUSC Hollings Cancer Center.

Immunotherapy is not easy for most patients to go through. It can cause autoimmune disease-like symptoms, swelling, pain, a rash, weight gain, diarrhea and other problems.

But Li says in some cases, it’s well worth the discomfort. 

“Right now, there’s a renewed sense of urgency,” Li said. “It’s a wholesale revolution, not just helping a handful of people. We’re moving the field forward.”