Pairing a novel personalized cancer vaccine with an established immunotherapy drug administered to patients in a new way, Harvard Medical School scientists at Dana-Farber Cancer Institute are testing a first-of-its-kind strategy aimed at improving outcomes for kidney cancer patients who are at high risk of recurrence following surgery.
This two-pronged approach to mobilizing a patient’s immune response against cancer cells that remain in the body after surgery, and may be the culprit for recurrence, is being evaluated in a phase 1 clinical trial that aims to enroll 15 to 20 patients.
It is the first trial to evaluate a personalized cancer vaccine in patients with kidney cancer.
“These are patients who have high-risk disease, and have had it all surgically removed,” said David Braun, HMS clinical fellow in medicine at Brigham and Women’s Hospital, who is leading the trial with Toni Choueiri, Jerome and Nancy Kohlberg Professor of Medicine at HMS and Dana-Farber, and Patrick Ott, HMS associate professor of medicine at Dana-Farber, in collaboration with the Broad Institute of MIT and Harvard.
“There is no clear evidence of disease left in their body, but we know that up to half of them will eventually have disease recurrence” resulting from undetected residual tumor cells, Braun said. “Currently there are no good treatment options available for these patients” to decrease the chances of recurrence.
Kidney cancer patients have been treated with immunotherapy drugs known as checkpoint blockers, which free immune cells from the restraints that prevent them from attacking cancer cells. For many types of cancers, checkpoint blockers have successfully unleashed the immune system against even advanced stages of cancer and improved survival.
Checkpoint blockers by themselves are approved for the treatment of metastatic kidney cancer, but there are still many patients who do not benefit from these therapies, said Braun.
“When you just take off the brakes on the immune system, it doesn’t always target the tumor well, and sometimes it targets other organs in the body, which is why people have side effects,” Braun said.
The new approach is aimed at improving the success of immunotherapy for these patients by combining a checkpoint-blocking antibody, ipilimumab, with a second weapon—a personalized vaccine designed to recognize neoantigens, cancer-specific proteins that are present on the individual’s cancer cells but not on normal cells.
The vaccine, known as NeoVax, is based on research at Dana-Farber led by Catherine Wu, HMS professor of medicine at Dana-Farber. Braun said that such a vaccine could “steer” the immune response to focus tightly on the cancer cells after being freed by the checkpoint blocker drug.
The DNA code of each patient’s tumor contains changes, or mutations, that make the tumor look foreign to the immune system, and those mutations differ from one patient to the next. The mutations cause the tumor cells to produce neoantigens which, like the mutations, are specific to the cancer cells of an individual patient.
To make a personalized neoantigen vaccine, samples of a patient’s tumor are analyzed to determine which neoantigens are present on the tumor cells. Then computational methods are used to predict which neoantigens are most likely to provoke a response by the immune system.
These neoantigens are then incorporated into a personalized vaccine designed to guide the immune system to attack cancer cells bearing those neoantigens.
Braun said, “Our hope is that if we can learn how to make immune therapy work effectively in this tumor type, then we will also learn lessons that are more broadly applicable to other types of cancer as well.”