Accession Number:

ADA556176

Title:

Development Of A Vaccine Targeting Triple-Negative Breast Cancer

Descriptive Note:

Annual summary 1 Sep 2010-31 Aug 2010

Corporate Author:

SEATTLE UNIV WA

Personal Author(s):

Report Date:

2011-09-01

Pagination or Media Count:

9.0

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. 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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE