Accession Number:

ADA592218

Title:

Development of a Vaccine Targeting Triple-Negative Breast Cancer

Descriptive Note:

Annual summary 1 Sep 2010-31 Aug 2013

Corporate Author:

SEATTLE UNIV WA

Personal Author(s):

Report Date:

2013-11-01

Pagination or Media Count:

29.0

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 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.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE