Vaccine Candidate for HER2 Breast Cancer Shows Promise at Duke
VRP-HER2 vaccine increased HER2-specific memory CD8 T cells and had anti-tumor effects in preclinical and clinical studies
In a small, phase 1 clinical trial conducted at Duke Cancer Insitute, a cancer vaccine candidate named HER2 VRP, demonstrated an ability to halt tumor growth and improve survival for a subset of patients.
These Duke researchers constructed a vaccine candidate using a neutralized virus vector to carry genetic information that targets HER2 proteins. Once deployed, the vaccines home in on the HER2 proteins in the cancer cells, sparking the immune system to mount an attack on the cancer.
Initially, in mouse models, the vaccine prompted tumors to recede, leading to a phase 1 clinical trial of 22 women, that began enrolling HER2-positive breast cancer patients between 2012 and 2015.
The first 4 patients received the vaccine only; all subsequent participants received the vaccine along with HER2 targeted therapies, which resulted in a more robust response to the vaccine.
Among study participants, 7 saw their tumor growth stabilize, at least initially. Two patients continue to survive at publication and have experienced long-standing control over tumor progression.
The researchers also identified a marker that correlates with improved progression-free survival.
“Therapies targeting HER2 are widely used to treat breast cancers that overexpress the protein, but drug resistance is common, leading to progressive disease and death,” said H. Kim Lyerly, MD, professor of surgery, immunology, and pathology at Duke and senior author of a study published in the journal Clinical Cancer Research.
“We need new options, and our study shows that vaccine approaches could lead to an additional weapon in the arsenal,” said Dr. Lyerly in a press release.
“These data support the further testing of this vaccine platform in combination with immune checkpoint inhibitors like anti-PD1 to better engage the expanded T cell populations,” Dr. Lyerly said.
HER2 is a protein that is overexpressed in 20-30% of breast cancers. It is also found associated with lung, gastric, ovarian, and pancreatic cancers.
Although there are existing therapies that can target HER2, most patients will eventually experience progression of their disease even though their cancer continues to express HER2, said this research.
Therefore, new approaches are needed for treating tumors that express HER2.
A phase 2 trial is being planned at Duke.
The work received funding support from the Department of Defense, Susan G. Komen Foundation, the National Center for Research Resources, the National Center for Advancing Translational Sciences and the National Institutes of Health.
These researchers did not disclose any conflicts of interest.
Corresponding Author: Herbert Kim Lyerly, Surgery, Duke University Medical Center, E-mail: [email protected]
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