An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply
Abstract
In an effort to meet the urgent need for the development of novel and effective treatments for metastatic breast cancer, we developed and evaluated a novel, oral DNA vaccine targeting endoglin (CD105). This target molecule, overexpressed on proliferating endothelial cells in the breast tumor neovasculature, proved most efficacious as this vaccine specifically activated antigen-presenting dendritic cells (DCs), induced effective immune responses by CD8+ T cells against endoglin-positive target cells and markedly suppressed tumor angiogenesis. We could prove by in vivo immunodepletions that the vaccine, delivered by gavage with attenuated Salmonella typhimurium to Peyer's patches in the small intestine, specifically activated CD11c+ OCs and their costimulatory molecules CD8O and CD86 as well as CD8+ T cells. Together, these effects led to a strong suppression of pulmonary metastases of D2F2 breast carcinoma cells in a syngeneic mouse tumor model. It is anticipated that this new vaccine strategy can be translated to clinical application to evaluate its use for the treatment of breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2007
- Accession Number
- ADA474671
Entities
People
- Ralph A. Reisfeld
Organizations
- Scripps Research