����TV

In his 57 years, Gary Keblish had never paid much attention to the large, dark mole on his lower right back. But one day in the spring of 2019, a colleague at the Brooklyn public high school where he teaches pointed out a red spot on Keblish’s shirt. In a bathroom mirror, Keblish saw that the mole was seeping blood. He consulted Peter A. Saitta, MD, an ����TV Langone dermatologist, who biopsied the lesion. To Keblish’s dismay, the finding was melanoma, a deadly form of skin cancer diagnosed in more than 91,000 Americans annually.

Dr. Saitta referred Keblish to surgical oncologist Richard L. Shapiro, MD, who performed an exploratory operation to determine how far the disease had spread to surrounding tissue. Dr. Shapiro found and removed a small mass under Keblish’s right arm. But Keblish was not out of the woods yet. When caught early, melanoma is highly treatable, but once it starts to migrate, as in Keblish’s case, the danger rises. Among patients diagnosed when the cancer has spread to nearby lymph nodes, about 74 percent are still alive five years later. For people with metastatic disease, however, the survival rate drops to 35 percent.

To boost his odds, Keblish was referred to medical oncologist Jeffrey S. Weber, MD, PhD, deputy director of Perlmutter Cancer Center at ����TV Langone. Dr. Weber is at the forefront of those working on a new generation of experimental treatments for melanoma aimed at preventing recurrence in patients who’ve had a tumor surgically removed. He offered Keblish a testing a new type of cancer vaccine using the same mRNA technology that would later be adapted for COVID-19 vaccines. 

Keblish hesitated. “I thought someone younger, who had more years to look forward to, might be a better candidate,” recalls the former marine, whose service in the first Gulf War helped prepare him for challenges ahead. But at the urging of his wife and teenage daughter, he decided to go for it.

Although researchers have tested cancer vaccines for decades, none had proven useful clinically. The vaccine in Dr. Weber’s trial, however, took a novel approach. Developed jointly by the pharmaceutical companies Moderna and Merck, it trained the immune system to attack neoantigens—proteins unique to the patient’s cancer. After Keblish’s tissue samples were genetically sequenced, technicians created a vaccine that was customized for his cancer and would target those proteins.

“I feel incredibly lucky to have participated in this trial. It’s given me the freedom to plan for the future.”
—Gary Keblish

Keblish was one of 107 trial participants who received both checkpoint inhibitors—an older class of immunotherapy that prevents cancer cells from disarming the immune system—and the personalized vaccine. When Dr. Weber and his team announced their results in April 2023 at the annual meeting of the American Association for Cancer Research, the news made global headlines. For the first time in a randomized trial, mRNA technology was shown to impact outcomes for melanoma patients. Over three years, the dual therapy had reduced the likelihood of cancer recurrence by 44 percent, as compared with the group receiving the checkpoint inhibitor alone. Moreover, immune side effects were similar in both groups.

Now, four years after receiving the treatment, Keblish remains in remission. “I feel incredibly lucky to have participated in this trial,” he says. “It’s given me the freedom to plan for the future.”

Dr. Weber, too, is looking ahead. A phase 3 trial is planned to start later this year. He’s also excited by growing evidence that adding mRNA vaccines to checkpoint inhibitors can reduce the recurrence of other forms of cancer. That sentiment is not a strictly professional one. In March, Dr. Weber had surgery for pancreatic cancer, and he hopes to enter a vaccine trial after he completes chemotherapy.

“We’re going to keep chipping away until almost nobody has a recurrence,” he vows. “I may not live long enough to see it happen. But as that famous philosopher Frank Sinatra used to say, the best is yet to come.”