Vaccine Kills HER2-Positive Murine Breast Tumor Cells
DETROIT, Sept. 15 (MedPage Today) -- A vaccine against HER2-positive breast cancer consistently destroyed tumors in laboratory animals, investigators here reported.
Mice immunized with the vaccine developed antibody and T-cell responses that were associated with destruction of both drug-resistant and drug-sensitive tumor cells, Wei-Zn Wei, Ph.D., of Wayne State University, and colleagues reported in the Sept. 15 issue of Cancer Research.
Laboratory studies also showed that the vaccine protected animals regardless of the nature or extent of chromosomal aberrations in these HER2-expressing tumor cells.
"The immune response against HER2-positive receptors we saw in this study is powerful and works even in tumors that are resistant to current therapies," Dr. Wei said. "The vaccine could potentially eliminate the need to even use these therapies."
In treated breast cancer patients, HER2-positive tumors that are refractory to antibody and targeted therapies have begun to emerge. Whether HER2 DNA vaccination could overcome drug resistance had not been determined.
Dr. Wei and colleagues used a DNA vaccine consisting of modified rat neu DNA, an immunostimulant, and an inactive bacterial plasmid. Mice were immunized with the vaccine against HER2 or with a control injection. The mice then were inoculated with HER2-expressing tumor cells, including cell lines with chromosomal aberrations and induced resistance to anti-HER2 targeted therapy.
All animals that received the control immunization developed progressive tumors. In contrast, immunization with the neu DNA vaccine induced a robust antibody response and activation of killer T cells. The vaccine afforded protection against all of the HER2-expressing cells.
"[The DNA vaccine] protected mice from neu-expressing tumors, regardless of their chromosomal aberration or resistance to neu-targeted therapy," the authors said.
In additional lab studies, the investigators demonstrated that the vaccine's activation of cytotoxic T cells was responsible for destroying tumor cells. Vaccine-induced antibody response was not required to kill the cells.
The study was supported by the National Institutes of Health. None of the authors reported any potential conflicts of interest.
Primary source: Cancer Research Source reference: Whittington PJ et al. "DNA vaccination controls Her-2+ tumors that are refractory to targeted therapies" Cancer Res 2008; 68: 7502-7511.
What breastcancer.org says about this article…
Vaccine Kills HER2-Positive Murine Breast Tumor Cells
HER2-positive breast cancers have too many copies of the HER2/neu gene. The study reviewed here gave an experimental vaccine that targets the HER2/neu gene to mice. When the mice were later injected with HER2-positive cancer cells, their immune systems destroyed the cancer cells.
While this research shows promise, this study was done in mice, not people. Much more work needs to be done before a human vaccine is available.
About 25% to 30% of all breast cancers are HER2-positive. HER-positive breast cancers tend to be more aggressive than HER2-negative breast cancers. Herceptin (chemical name: trastuzumab) and Tykerb (chemical name: lapatinib) are targeted therapy medicines that treat HER2-positive advanced-stage breast cancers. Herceptin also is used to treat HER2-positive early-stage breast cancer after surgery to reduce the risk of the cancer coming back.
Still, many HER2-positive breast cancers either don't respond or stop responding to targeted therapies. This is one reason why doctors continue to look for better ways to treat HER2-positive breast cancer.
Vaccines train the immune system to react to a specific target by exposing the immune system to the target or a weakened version of the target.
The vaccine in this study targeted the HER2/neu gene and contained:
- a modified version of part of the HER2/neu gene
- particles that deliver the gene bits to the mouse immune system (called plasmids)
- substances that stimulate the immune system
When the mice immune systems responded to the vaccine, they made antibodies and T-cells. Antibodies and T-cells are special immune factors that seek out and destroy the targeted invaders. So when the mice were injected with HER2-positive cancer cells, their immune systems were ready to produce large amounts of antibodies and T-cells that attacked the cancer cells.
Another preliminary study showed that women being treated for HER2-positive breast cancer who also received an experimental HER2 cancer vaccine, called NeuVax, were more likely to be alive 2 1/2 years later compared to women who didn't get the vaccine.
In a sense, vaccines rev up your immune system so it better protects you against disease or is better at fighting any disease you already have. Much research still needs to be done, but there is hope that vaccines will be effective in both preventing and treating cancer, including breast cancer.
Stay tuned to Breastcancer.org for the most up-to-date news on vaccines and other new approaches to breast cancer prevention and treatment.
