A New Approach to a Breast Cancer Vaccine

 Joseph Baar, MD, PhD

Attempts to develop a breast cancer vaccine have repeatedly met with failure because the cancer cells evade immune cells, either by changing or not expressing the molecular targets that the immune cells seek. Joseph Baar, MD, PhD, Director of Clinical Breast Cancer Research at UH Seidman Cancer Center and Associate Professor of Medicine, Case Western Reserve University School of Medicine, is piloting a new approach for select women with metastatic breast cancer – a vaccine targeting tumor blood supply.

“Our vaccine offers a new strategy, targeting elements on the surface of the vasculature,” Dr. Baar says. “That’s the novel thing about it. The vaccine has an additional potential advantage: It may be useful in many types of metastatic breast cancers because it focuses on the vasculature, not tumor-specific markers.”

This approach has been used with other cancers, but Dr. Baar and his team are the first to attempt it with breast cancer.

Dr. Baar and his team are using dendritic cells to generate killer T cells for the investigational vaccine. Dendritic cells are the most potent antigen-presenting cells for generating sensitized T cells. Appropriate antigens are loaded onto dendritic cells, which are then injected into patients to create a specific immune response.

“We are using a tumor blood vessel antigen (TBVA) peptide-pulsed dendritic cell vaccine (alphaDCI) to immunize patients,” Dr. Baar says. “Patients must be HLA-A2 positive because the TBVA peptides are specific for HLA-A2 molecules and do not bind to other HLA molecules. However, because 40 to 50 percent of the general population is HLA-A2 positive, we shouldn’t be too limited in the women we can treat.”

To avoid the problem of patients’ regulatory T cells and myeloid-derived suppressor cells dampening the desired immune response, Dr. Baar is administering the chemotherapy agent gemcitabine to all trial participants before giving the vaccine. “This agent has proven effective in down-regulating the activity of these cells and mediating an enhanced response to immunotherapy,” he says. “By knocking out the immune suppressor cells first with the chemotherapy and then coming in with the vaccine when the immune suppressor cells have been cleared out, we’re hoping the vaccine will have more effect.”

Dr. Baar and his team recently completed generating the necessary dendritic cells for the 15 participants with metastatic breast cancer who will receive the investigational vaccine. The pilot study has been approved by the University Hospitals Institutional Review Board and is scheduled to enroll its first patient in early 2016.

For Dr. Baar, the hope is that the vaccine will provide a more effective treatment for women who have limited options.

“Most of the women we’ll be seeing will have failed prior chemotherapy,” he says. “Instead of putting them on another chemotherapy regimen, we’re going to try get their cancer under control with this combined chemotherapy/immunotherapy approach.”

For more information on this new trial for women with metastatic breast cancer at UH Seidman Cancer Center or to refer a patient, email Sonia.Vasil@UHhospitals.org.

All National Institutes of Health (NIH) funding for basic and clinical research is awarded to the School of Medicine at Case Western Reserve University.