Cancer Breakthroughs

But new immunotherapy drugs that can unleash a patient’s own immune system are changing the outlook for treatment of the most difficult cancers.

An Emory scientist’s groundbreaking discoveries pointed the way to the new therapies, and clinical investigators at Emory’s Winship Cancer Institute have been involved in clinical trials of almost every immunotherapy drug approved by the US Food and Drug Administration (FDA).

When Danny Foshee was diagnosed with lung cancer in 2014, the disease was already too advanced for surgery. Foshee met with Suresh Ramalingam, Winship deputy director and director of medical oncology, and Rathi Pillai, the medical oncologist who would become Foshee’s primary Winship physician. After reviewing his case, they asked Foshee if he would like to be considered for a clinical trial that compared the effectiveness of traditional chemotherapy and a new immunotherapy treatment designed to strengthen the immune system’s ability to recognize and fight cancer cells.

To be eligible for the appropriate trial, Foshee needed to have one of three biomarkers on his tumor cells. Only days before the trial closed to new patients, he tested positive for high levels of PD-L1.

Producing the protein PD-L1 is one way cancer outsmarts the immune system. On noncancerous cells, PD-L1 signals the immune system not to attack. That can be very useful, for example, during pregnancy when PD-L1 plays an important role in immune system tolerance of the fetus. But when cancer cells produce PD-L1, its presence on the cells tricks the immune system into not recognizing an enemy that should be attacked. Patients with high levels of PD-L1 in tumor cells—and in the immune cells surrounding lung tumors—often do not respond as well to treatment.

Foshee’s high levels of PD-L1 made him eligible for a clinical trial studying nivolumab, a new drug that blocks PD-1, the receptor to which PD-L1 binds. Two months after immunotherapy began, his tumors had reduced in size by half. Ongoing scans show increasing shrinkage and no spread of cancer. His worst side effect has been some itching.

While the trial was ongoing, the FDA approved nivolumab for patients with metastatic, non-small cell lung cancer resistant to chemotherapy, which described Foshee. Ramalingam, a national leader in clinical trials for lung cancers, directed one of the two trials as well as several others at Winship.

Use of immunotherapy is likely to expand for lung cancer patients, says Ramalingam. Certain lung cancers are among the most responsive, equaled only by melanoma.

But while new drugs like nivolumab are game changers for patients like Foshee, there are many more patients for whom the drugs are not effective. Ramalingam’s goal is to develop biomarkers to predict which patients will respond to which drugs and what can be done to turn nonresponders into success stories.

Wally Curran, executive director of Winship Cancer Institute, says science has understood for years that the patient’s own immune system has the potential to control cancer. In the past decade, he says, “we have discovered how to unlock the patient’s own immune system, enabling T cells to identify cancer as a foreign agent—and we are doing it with less or no toxicity.”—Sylvia Wrobel