An experimental breast cancer vaccine safely generated an immune response to human epidermal growth factor receptor 2 in a phase 1 study.
Vaccination with an intermediate dose was associated with immunity in most patients.
The vaccine is undergoing a phase 2 trial.
In women with metastatic breast cancer, an experimental vaccine against human epidermal growth factor receptor 2 (HER2) safely generated an immune response to the protein. This is according to results from a phase 1 non-randomized study published in JAMA Oncology.
Because this was not a randomized clinical trial, the results should be considered preliminary. However, as lead author Mary “Nora” L. Disis, MD, said, speaking for the news release about the study, “the findings are promising enough that the vaccine will now be evaluated in a larger, randomized clinical trial.”
This study is a step forward in the quest to develop an effective vaccine to treat patients with breast cancer.
Vaccine studies to date
In a 2022 review, Dr. Disis and colleagues noted that several breast cancer vaccines have advanced to phase 2 or phase 3 trials, but these trials have not met progression-free or overall survival primary endpoints.
Despite the disappointing results, researchers have gained valuable information on the clinical application of the vaccines, from the type of immune response needed to eradicate a tumor or induce type I T-cell immunity, to the patient populations for whom vaccination would be most beneficial.
Some researchers have speculated that the anti-tumor immunity stimulated by vaccines does not last long enough to significantly affect survival. To overcome this issue, such factors as the optimal dose and schedule for immunization, delivery routes, and choice of immunologic boosters need to be investigated.
Vaccine targets: HER2 and ERBB2 ICD
HER2-targeted therapy is one avenue of investigation for a breast cancer vaccine.
The overproduction of HER2 is found in as many as 30% of breast cancers. HER2-positive breast cancers tend to be both more aggressive and more likely to recur post-treatment than HER2-negative breast cancers.
Some patients mount an immune response to the high levels of HER2, and especially to overproduction of its erb-b2 receptor tyrosine kinase 2 (ERBB2) intracellular domain (ICD). This immune response, which is cytotoxic, is beneficial: it results in less chance of recurrence and longer overall survival.
Favorable clinical outcomes after trastuzumab therapy have, in fact, been reported in patients with high levels of ERBB2–specific type 1 T cells in the peripheral blood, according to Dr. Disis and her investigative team.
Only a minority of patients develop this ERBB2 immunity post-treatment, however.
The investigators proposed that, if a vaccine were designed to increase ERBB2-specific T-helper cells, this could induce ERBB2 immunity in more patients.
To test this hypothesis, Dr. Disis and colleagues developed a DNA vaccine encoding the ERBB2 ICD.
DNA vaccine: Phase 1 trial
As reported in JAMA Oncology, Dr. Disis and her team tested the safety and the immunogenicity of the DNA vaccine at three different doses in a single-arm study.
For the study, 66 women (median age, 51 years) with advanced-stage ERBB2-positive breast cancer were enrolled. All were treated at the University of Washington School of Medicine between 2001 and 2010.
The participants were divided into three dose groups, to receive intradermal monthly vaccine injections of low-dose (10 μg), intermediate-dose (100 μg), or high-dose (500 μg) formulations. Each participant received three injections. Participants also received the immune-stimulating drug granulocyte-macrophage colony-stimulating factor, which promotes cytotoxic immunity.
Median follow-up was nearly 10 years. The researchers evaluated toxicity at set intervals and yearly. Immunity was assessed via the collection of peripheral blood mononuclear cells, and vaccine sites were biopsied at weeks 16 and 36 to measure DNA persistence.
Most of the adverse events related to the vaccine were grade 1 and 2 events and occurred with all doses.
"The results showed that the vaccine was very safe."
— Mary “Nora” L. Disis, MD
“In fact, the most common side effects that we saw in about half the patients were very similar to what you see with COVID-19 vaccines: redness and swelling at the injection site and maybe some fever, chills and flu-like symptoms,” Dr. Disis said.
After adjustment for baseline factors, patients in the 100-μg group and the 500-μg group had higher-magnitude ERBB2 ICD type 1 immune responses than the 10-μg group at most time points. Immunity decreased with DNA persistence at the injection site, and the highest incidence of persistent DNA was seen with the highest vaccine dose.
In summing up the study results, the authors stated that immunization with 100 μg of ERBB2 ICD plasmid DNA was associated with generation of immunity in most patients, which persisted after the end of vaccinations.
Phase 2 study initiated
The vaccine is undergoing a phase 2 study.
If the results of the new randomized, controlled phase 2 study of the vaccine are positive, “it will be a strong signal” to rapidly move forward to a definitive phase 3 trial, noted Dr. Disis.
"I have high hopes that we’re close to having a vaccine that can effectively treat patients with breast cancer."
— Mary “Nora” L. Disis, MD
What this means for you
The experimental breast cancer vaccine encoding the ERBB2 ICD safely generated an immune response in patients with metastatic breast cancer. However, the findings should be considered preliminary.
For more information or enrollment inquiries for the phase 2 study, contact the patient coordinator at email@example.com or 206-543-3829