After Giving Up on Cancer Vaccines, Doctors Start to Find Hope

Marilynn Duker knew her family tree was dotted with relatives who had cancer. So when a genetic counselor offered her testing to see if she had any of 30 cancer-causing gene mutations, she readily agreed.

The test found a mutation in the gene CDKN2A, which predisposes people who carry it to pancreatic cancer.

“They called and said, ‘You have this mutation. There really is nothing you can do,’” recalled Ms. Duker, who lives in Pikesville, Md., and is chief executive of a senior living company.

She began having regular scans and endoscopies to examine her pancreas. They revealed a cyst. It has not changed in the past several years. But if it develops into cancer, treatment is likely to fail.

Patients like Ms. Duker don’t have many options, noted Dr. Elizabeth Jaffee, deputy director of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University. A person with more advanced cysts could avoid cancer by having their pancreas removed, but that would immediately plunge them into a realm of severe diabetes and digestive problems. The drastic surgery might be worthwhile if it saved their lives, but many precancerous lesions never develop into cancer if they are simply left alone. Yet if the lesions turn into cancer—even if the cancer is caught at an early stage—the prognosis is grim.

But it also offers an opportunity to make and test a vaccine, she added.

In pancreatic cancer, Dr. Jaffee explained, the first change in normal cells on the path to malignancy almost always is a mutation in a well-known cancer gene, KRAS. Other mutations follow, with six gene mutations driving the cancer’s growth of pancreatic cancer in the majority of patients. That insight allowed Hopkins researchers to devise a vaccine that would train T cells — white blood cells of the immune system — to recognize cells with those mutations and kill them.

Their first trial, a safety study, was in 12 patients with early stage pancreatic cancer who already had been treated with surgery. Although their cancer was caught soon after it had emerged and despite the fact that they were treated, pancreatic cancer patients typically have a 70 percent to 80 percent chance of having a recurrence in the next few years. When pancreatic cancer returns, it is metastatic and fatal.