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. No toxicities were associated with vaccination targeting IGFIR. Through vaccination, high levels of IGF-IR-specific 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
- Nov 01, 2013
- Accession Number
- ADA592218
Entities
People
- Denise Cecil
Organizations
- Seattle University