Development of a Novel Multi-Antigen Breast Cancer Prevention Vaccine for Premalignant Disease
The overall goal of this research project is to provide empirical support for a future clinical trial of a novel breast cancer prevention vaccine in women with benign breast disease.
This vaccine is designed to drive immune responses to subdominant epitopes of six breast cancer proteins: HER2, mammaglobin, MAGEA3, hTERT, MUC1 and survivin. The vaccine will be studied in a clinical trial of women with breast cancer. Immune responses to the vaccine will be studied in detail. In addition, we will study breast tissue from women with breast cancer and tissue from benign breast biopsies they had years before developing cancer. This will help determine whether early expression of the vaccine antigens is present and is linked to later cancer development.
Hypotheses
We hypothesize that:
- Elevated expression of the six vaccine-targeted antigens in benign breast disease tissue is associated with higher risk of breast cancer and correlates with antigen expression in future breast cancers.
- The novel vaccine induces robust peripheral immune responses, engaging multiple T cell phenotypes (such as Th1, Th17 and Th2) and antibody-producing B cells.
- Vaccine delivery results in immune responses in breast lobules with antigen expression.
Project aims
- Aim 1: Determine frequency of expression of the prevention vaccine-targeted antigens in benign breast disease tissue and which antigens are associated with progression to breast cancer.
- Aim 2: Evaluate blood-based biomarkers of response to the multi-antigen vaccine.
- Aim 3: Define the response to multi-antigen vaccine exposure in benign breast tissue (target antigens, immunologic profiles and their associations).
Project co-leaders