First Steps: Vaccine Research

While Provenge is the first and only FDA-approved vaccine to treat cancer, researchers and patients hope it won’t be alone for long. Edgar Engleman, MD, professor of pathology and medicine at Stanford University who was involved in work that eventually resulted in Provenge, said it took years of research and development before it was finally approved because it represented a whole new paradigm.

“In the 20 years since that work was done, there has been a great deal of encouragement and excitement about therapeutic cancer vaccines—and with the idea that we can make things better, that Provenge is just the first step,” he says. A number of vaccines are in the pipeline for a variety of cancers, and while they are all considered vaccines, they work quite differently from one another.

Researchers have had promising results with a peptide vaccine called AE37 in early-stage, HER2-positive breast cancer. This vaccine can induce an immune reaction and is being tested to prevent recurrence. Plans for a phase 3 trial are under way. (AE37 is also being studied in prostate cancer.)

Another vaccine, Neuvax, which uses the E75 peptide, is being tested in a phase 3 trial for low HER2-expressing tumors.

While most theories lean toward administering vaccines in patients with early-stage disease—before the disease becomes resistant—that strategy proves harder to do in cancers such as lung, pancreatic and liver, which are often diagnosed in later stages. However, there are several vaccines for non-small cell lung cancer that appear to have merit.

Results of an early trial for TG4010 combined with chemotherapy showed more patients had progression-free survival at six months than patients on chemotherapy alone. And while overall survival didn’t change much as a whole, researchers believe the vaccine may enhance the chemotherapy’s effect in patients with normal levels of certain biomarkers. A phase 2b/3 trial is now under way.

A phase 3 study of rindopepimut is currently ongoing for patients with a type of glioblastoma that has a mutated version of the EGFR protein. In this particular study, the vaccine is being combined with Temodar (temozolomide), a standard of care for this aggressive brain tumor. Rindopepimut is also being tested in combination with Avastin (bevacizumab) in a phase 2 study. Combining vaccines with currently available targeted agents or chemotherapy is a technique that scientists are hoping will pay off.

“Most experts in the field believe that combinations of drugs that target different components of the tumor and use different mechanisms to target the tumor will be the answer,” Engleman says. “The idea of combining the targeted drug therapy with targeted immunotherapy makes a lot of sense.”

Although most vaccines focus on one particular target, a myeloma vaccine is created from two protein fragments, or peptides. MAGE-A3 and NY-ESO-1 are common proteins expressed in myeloma cells. The thought behind using both is to teach the immune system to attack cancer cells that present one or both of these peptides.

For every promising vaccine study, there are more that have failed. Researchers have welcomed the era of cancer vaccines, but further study is needed to determine the best types of vaccines, at what stage to administer them and how, and ways to improve cost effectiveness.

[Find vaccine clinical trials at ClinicalTrials.gov]