For half a century, researchers have dreamed of giving cancer patients a vaccine that helps the immune system detect the tumors as foreign tissue and wipe them out. Now, a new approach that tailors a personalized vaccine to the mutated proteins in an individual’s tumor appears to have prevented early re-lapses in 12 people with skin cancer.
“We’re in this very exciting, new moment” for personalized cancer vaccines, says Catherine Wu of the Dana Farber Cancer Institute in Boston, whose team presented results last week at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D. C. A second team has similarly encouraging data. The two small studies, mainly designed to test safety and immune responses, are indeed “promising, “says Drew Pardoll of Johns Hopkins University in Baltimore, Maryland. But, he cautions, it is “way too early” to draw firm conclusions about whether the vaccines will extend the lives of cancer patients.
Whereas earlier, unsuccessful cancer vaccines usually targeted a single distinctive cancer protein shared among patients, these new ones contain multiple mutated proteins, or “neoantigens, “that are specific to an individual patient’s tumor. Giving patients a dose of their tumor neoantigens, which look foreign to the immune system, should help activate immune cells called T cells to attack the cancer cells.
One new study was conducted in six patients with melanoma that had spread to their lymph nodes and sometimes other sites. The patients’ tumors had been removed surgically, but were likely to regrow. Wu’s team sequenced the DNA from each patient’s tumors and used computational methods to predict mutations that coded for neoantigens. Then they made each patient a personal vaccine containing about 20 of these neoantigens. The researchers injected the vaccine under the patients’skin periodically for 5 months. They had no serious side effects and showed “strong, potent T cell responses” specific to many of their vaccine neoantigens. All are now cancer-free up to 32 months later.
The two patients with the most advanced disease did relapse, but Wu’s team deployed an additional weapon. an immunotherapy drug called a PD-1 checkpoint inhibitor. These antibody drugs block receptors on T cells that tumors use to hide from the immune system. On their own, the drugs have vanquished tumors in people with certain cancers who otherwise had no hope.
Similar results come from an international trial using a vaccine developed by Ugur Sahin of University Medical Center of Johannes Gutenberg University in Mainz, Germany. The team injected RNA coding for up to 10 tumor neoantigens into the lymph nodes of 13 advanced melanoma patients whose tumors had been removed. Eleven remain cancer-free up to 26 months later, including two whose tumors reappeared, then shrank or were surgically removed, Sahin says. Another patient whose cancer returned received a PD-1 inhibitor and is also tumor-free.
Pardoll and others caution, however, that it’s not possible to know whether neoantigen vaccines per-form better than a PD-1 inhibitor alone without doing larger studies. Other questions remain about how best to design and deliver neoantigen vaccines. Right now the vaccines are costly and take months to make, which may be too long for some patients with metastatic disease.
Meanwhile, several biotech companies are launching trials combining neoantigen vaccines and check-point inhibitors for various cancers. The Parker Institute for Cancer Immunotherapy in San Francisco, California, launched a year ago by Napster co-founder and biotech billionaire Sean Parker, is trying to figure out how to tailor the best possible vaccines through a competition.
What is new of the tumor vaccines in Professor Wu s study?
They are personalized with multiple mutated proteins to protect patients.
They are more powerful on the base of new single proteins.
They are experimented on humans instead of animals only.
They are about to be massively produced to be clinically used.
A