from Dana Farber 1/2019
By pairing a novel personalized cancer vaccine with a more established immunotherapy drug that is administered to patients in an innovative fashion, 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 patients’ immune response against cancer cells that remain in the body after surgery (and may be the culprit for the cancer coming back later) 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, MD, PhD, who is leading the trial in a 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. “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 restraints that prevent it from attacking cancer cells. For many types of cancers, checkpoint blockers have successfully unleashed the immune system
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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.”
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 cancer-specific proteins, called neoantigens, 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. Braun said that such a vaccine could “steer” the immune response – after being freed by the checkpoint blocker drug – to focus tightly on the cancer cells.
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 the tumor taken from the patient 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 that is 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 that we will also learn lessons that are more broadly applicable to other types of cancer as well.”