Duke University scientists are working on a potential breast cancer vaccine using the innovative mRNA technology that enabled rapid development of COVID-19 vaccines, Fox News reported.
The scientists explained in a paper on their research that they are employing the technology to combat a type of breast cancer that overexpresses a protein called HER2, which is the driver of HER2-positive breast cancer and the cause of about 20% of all breast cancer cases.
“It is a product which is RNA nucleic acid which encodes a specific protein and then that can be encapsulated in something we like to call a lipid nanoparticle, which is really a little fat bubble, and that can be injected into your body and sort of teaches your body what to go after immunologically,” Dr. Zachary Hartman, assistant professor in the departments of surgery, pathology, and immunology at Duke University School of Medicine explained.
According to their 2019 paper published in Clinical Cancer Research, the team “constructed a vaccine based on a novel alphaviral vector encoding HER2 and tested it in Phase 1 clinical trial, where we demonstrate that it was well tolerated with no dose-limiting toxicity. Preclinical models additionally demonstrate immunogenicity and antitumor activity of the vaccine.”
The Phase 1 clinical trial “found potential with a vaccine that induced anti-tumor growth in seven of the 22 patients who had recurrent breast cancer, with two continuing to survive at the time of the published research,” according to an updated July 9, 2019 press release.
Dr. Herbert Kim Lyerly, M.D., professor of surgery, immunology, and pathology at Duke and senior author of a study in the journal Clinical Cancer Research, told Fox “the HER2 protein, which is associated with aggressive tumor growth, goes on overdrive in 20% to 30% of breast cancers, so treatments are targeted against this protein, but drug resistance limits its use.”
Lyerly and colleagues, including lead author Erika J. Crosby, Ph.D., and Hartman, constructed a vaccine using a neutralized virus vector—a novel alphaviral vector encoding a portion of HER2 (VRP-HER2)—to carry genetic information that targets HER2 proteins.
“Once deployed, the vaccines homes in on the HER2 proteins in the cancer cells, sparking the immune system to mount an attack on cancer,” the press release said.
‘One-two punch’ with a checkpoint inhibitor
But “while the vaccine works to a degree on its own, the tumor can still activate backup strategies for survival”, a 2020 Duke press release explains, adding that “when combined with existing immune checkpoint inhibitors, the one-two punch proves highly effective.”
According to the release, “the treatment with the investigational vaccine was significantly enhanced when combined with the checkpoint inhibitor drug pembrolizumab,” which has shown limited benefit for HER2-positive breast cancers when used alone.
By working in tandem, “the vaccine primes the immune system and the checkpoint inhibitor then rallies the T-cells to action, resulting in pronounced tumor reduction and long-term tumor-free survival,” said the 2020 Duke press release. “The HER2 targeted vaccine in combination with pembrolizumab is currently in a Phase 2 study at Duke and is led by Lyerly, Michael Morse, and Jeremy Force.”
The vaccine is being tested on 39 women, and results are expected later this year.
Lyerly told Fox News that although the current synthetic mRNA vaccine is directed against breast cancer, “it can be used for other cancers that express the HER2 protein, including lung cancer, stomach, and esophageal cancer.”
