Immunotherapy: The next frontier in cancer treatment?

In In The News by Barbara Jacoby

LLH network pressFrom MedCity News


Though radiation sent Coris Shepard to the hospital with a burned esophagus for 21 days, it did little to the tumors in his left lung. The chemotherapy that followed didn’t work either. In fact, the stubborn cancer actually grew in size.

At wit’s end and almost out of hope, he agreed to participate in a clinical trial testing a new drug at Mount Sinai Comprehensive Cancer Center in Miami Beach, a drug that would use his body’s immune system to fight the cancerous cells. In April, four months after beginning treatment, an MRI determined some tumors had shrunk and others had disappeared entirely.

“I was absolutely elated,” says Shepard, who spends summers in Aventura and the rest of the year in Philadelphia. “I’m more hopeful now because nothing else I had tried had actually worked.”

Shepard is participating in Phase 1 of the MedImmune PD-L1 study. Mount Sinai is one of only four centers in the country where this treatment is available. The first part of the trial targets kidney, lung and colon cancers as well as deadly skin cancers known as melanomas. Researchers hope to open the study to head and neck cancer patients later. Like Shepard, the patients participating in the research are ones who have tried conventional treatments without success.

Shepard received infusions of an experimental treatment that uses the power of our body’s immune system to attack the cancer. The drug appears to work in a deceptively simple way, but it has taken years of research for scientists to tease out the information they needed to get this far.

Scientists now know that cancer cells use a cloaking mechanism to make themselves invisible to our immune system. They do this by binding together two proteins. One protein is called PD-1, or programmed death 1, which sits on T-cells, known as the warrior cells of our immune system. The second is a PD-L1, or programmed death ligand 1, which sits on the surface of the cancer cell to shield it from an attack by the body’s immune system. The treatment Shepard received targets PD-L1.

With this “shield” gone from the cancer cells, the tumor can no longer hide from the body’s immune system.

Mount Sinai medical oncologist Dr. Jose Lutzky says initial results show that treatment has successfully shrunk tumors, but he also warns that the experiment is at a very early stage. Phase 1 of clinical trials seeks to increase the doses of a drug very slowly to determine the optimal amount that does the most good with the least harm

“There are many steps involved in this process and we’re just beginning to discover them,” he said. “While we are seeing significant tumor shrinkage, we’re trying to find the right dose. We also know that the blockage offered by the cancer cells is going to vary from tumor to tumor.”

The MedImmune PD-L1 study is not the only one targeting the protein that enables cancer cells to make themselves invisible to the body’s immune system. Other companies, including Merck, Bristol-Meyers Squibb and Genentech/Roche, are developing drugs that target either PD-L1 or the molecule that binds to it (PD-1).

This kind of unprecedented effort underscores the research community’s enthusiasm for immunotherapy as the most promising new treatment for cancer. In fact, several immunotherapy drugs still in the testing phase were the talk of the American Society of Clinical Oncology meeting in Chicago in June. These new agents spur the body’s natural immune system to go after cancer cells, just as they would do in the case of a bacterial infection. What’s more, the concept has already been shown to work in a range of cancers. Provenge, the first cancer immunotherapy, was approved in 2010 to treat prostate tumors and Yervoy, approved a year later, treats metastatic melanoma.

“We’ll be looking for even more progress in this area,” Lutzky said. “I don’t think I’ve been so hopeful as an oncologist in a long time.”

Across town another promising immunotherapy is being studied at the University of Miami’s Miller School of Medicine. At the lab of Dr. Glen Barber, professor and chair of the Cell Biology Department, scientists are researching how a therapeutic virus known as vesicular stomatitis virus, or VSV, is able to destroy cancer cells while leaving normal healthy cells intact.

“All cancer cells are extraordinarily sensitive to viruses,” Barber said. “They have some kind of defect in that respect.”

Using the knowledge that cancers are susceptible to virus replication and thus are easily killed after an infection, Barber and his team tested it first on animal cells. Result? Normal cells didn’t allow replication of the VSV, but cancer cells actually exploded and died as a result.

“The virus,” Barber explained, “replicates like a balloon and pops the cancer cell.”

In the process of eliminating the virus infection “the body responds by eating the virus-infected cells. It cleans up and attacks the cancer cells,” he added.

Tested initially in mice, rats and rhesus monkeys, VSV is now in Phase I trials for the treatment of liver cancer at UM, in conjunction with the Mayo Clinic in Rochester, Minn., and Scottsdale, Ariz. This means scientists are using “very low doses, very conservative treatment” to determine both efficacy and lack of toxicity. Patients also receive an immune stimulatory gene, interferon beta, within the virus.

While encouraged by the progress of the experiment, Barber warns that the public shouldn’t expect an overnight cure. “It’s a tremendously complicated process and we have so much to unravel,” said Barber, who is also associate director of Basic Research at Sylvester Comprehensive Cancer Center. “There’s a lot of work going on and it takes time.”
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