Development of a Vaccine Targeting Triple-Negative Breast Cancer
Annual summary 1 Sep 2010-31 Aug 2013
SEATTLE UNIV WA
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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.
- Anatomy and Physiology
- Medicine and Medical Research