Therapeutic cancer vaccines are a growing area of immunology research. These vaccines activate tumor-specific immune cell responses to help the immune system identify and attack cancer cells. Several vaccines focusing on breast cancers that are positive for human epidermal growth factor receptor 2 (HER2) are being studied in clinical trials. Now researchers at Moffitt Cancer Center are working to develop a dendritic cell vaccine targeting HER3, a protein involved in the growth and spread of many different cancer types. Their pre-clinical work has been published in the journal Cancer Immunology Research.

HER3 is a member of the human epidermal growth factor receptor family. When overexpressed, HER3 can increase the likelihood that cancer will spread and cause treatment to fail. Several therapies that target HER3 are in clinical development; however, none that take advantage of the tumor fighting capabilities of the immune system to target HER3 are being tested. Given the role of HER3 in the development and progression of cancer, Moffitt researchers wanted to assess the possibility of developing a HER3-targeted dendritic cell vaccine to act as either a preventive or therapeutic strategy against different tumor types.

The researcher team first confirmed that HER3 was overexpressed in several types of cancer, including bladder, breast, lung adenocarcinoma, prostate and stomach, and was associated with poor survival in melanoma and pancreas cancer. They then identified nine short peptide sequences of the HER3 protein that could be used to generate an immune response from CD4+ T cells in both healthy donors and breast cancer patients. Importantly, the researchers reported that the sequences could be used among a broad patient population based on data from receptor binding studies.

To assess whether the vaccine could offer protection against the development of cancer or decrease the growth of existing tumors, the researchers vaccinated mice with HER3-peptide stimulated dendritic cells, then injected them with breast cancer or melanoma cells. Mice that were vaccinated with HER3-peptide stimulated dendritic cells had significantly delayed tumor growth and prolonged survival compared to mice that received control cells. Similarly, HER3-peptide stimulated dendritic cells also significantly delayed tumor growth and prolonged survival when injected into existing breast and melanoma tumors in mice, including a model of drug resistant breast cancer. The researchers confirmed that the HER3-peptide stimulated dendritic cells were producing immune responses mediated by CD4+ T cells and produced antitumorigenic cytokines.

“Developing HER3-specific cellular immunotherapy can be a novel and efficient treatment strategy for multiple cancer types overexpressing HER3 to improve patient prognosis and survival,” explained Brian Czerniecki, MD, PhD, chair of the Department of Breast Oncology at Moffitt.

More research is needed, but Czerniecki and his team hope to advance this discovery to human clinical trials in the future.

Their study was supported by the National Cancer Institute, Department of Defense and Pennies in Action.