Development Of A Vaccine Targeting Triple-Negative Breast Cancer
Annual summary 1 Sep 2010-31 Aug 2010
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. Thus, therapeutically targeting tumor cells which have upregulated IGF-IR may be a promising approach to treat TNBC. IGF-IR is immunogenic in breast cancer and is a potential target for active immunization. We sought to develop a vaccine that will elicit Th1 immunity to IGF-IR. Ninety-five percent of the peptides predicted to bind with high affinity to MHCII induced a Th1 immune response in human PBMC. However, since IGF-IR is a self tumor antigen, Th epitopes could potentially elicit either an inflammatory Th1 i.e. IFN-g or immunosuppressive Th2 i.e. IL-10 response. A ratio of magnitude and frequency of ELISPOT responses for IFN-g and IL-10 was calculated. The peptides that demonstrated a preference to secrete IFN-g over IL-10 were located primarily in the C-terminus of IGF-IR. Vaccination with those C-terminal peptides in a mouse model of TNBC demonstrated a robust Th1 response and concomitant inhibition of tumor growth. These data suggest that more effective peptide-based vaccines could be designed when both Th1 epitopes and immunosuppressive epitopes are screened simultaneously.
- Anatomy and Physiology
- Medicine and Medical Research