Development of a Vaccine Targeting Triple-Negative Breast Cancer
Abstract
The insulin-like growth factor (IGF) pathway plays an important role in breast cancer growth and metastasis. The IGF-I receptor (IGF-IR) is over-expressed in almost 50% of triple negative breast cancers (TNBC) and is associated with poor prognosis and drug resistance. Thus, therapeutically targeting tumor cells which have upregulated IGF-IR may be a promising approach to treat TNBC. We report that IGF-IR is immunogenic. Through vaccination, high levels of IGF-IR Th1 could be generated which elicited IFN-g-dependent breast cancer inhibition. SOCS1, upregulated by IFN-g, bound IGF-IR. This interaction inhibited receptor signaling, modulated additional oncogenic proteins, and increased PTEN expression. Oncogenic shock, induced by immunization, restored sensitivity to Tamoxifen therapy in mice refractory to treatment. Cytokine mediated oncogenic shock may be a mechanism by which cancer vaccines, or other immunotherapies, improve response to subsequent standard treatments resulting in a survival benefit in cancer patients treated with immune modulatory approaches.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2012
- Accession Number
- ADA567745
Entities
People
- Denise Cecil
Organizations
- University of Washington