Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes

S. D. Soysal, S. Muenst, J. Kan-Mitchell, E. Huarte, X. Zhang, I. Wilkinson-Ryan, T. Fleming, V. Tiriveedhi, T. Mohanakumar, L. Li, J. Herndon, D. Oertli, S. P. Goedegebuure, W. E. Gillanders

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Mammaglobin-A (MAM-A) is a secretory protein that is overexpressed in 80 % of human breast cancers. Its near-universal expression in breast cancer as well as its exquisite tissue specificity makes it an attractive target for a breast cancer prevention vaccine, and we recently initiated a phase 1 clinical trial of a MAM-A DNA vaccine. Previously, we have identified multiple MAM-A CD8 T cell epitopes using a reverse immunology candidate epitope approach based on predicted binding, but to date no attempt has been made to identify epitopes using an unbiased approach. In this study, we used human T cells primed in vitro with autologous dendritic cells expressing MAM-A to systematically identify MAM-A CD8 T cell epitopes. Using this unbiased approach, we identified three novel HLA-A2-restricted MAM-A epitopes. CD8 T cells specific for these epitopes are able to recognize and lyse human breast cancer cells in a MAM-A-specific, HLA-A2-dependent fashion. HLA-A2+/MAM-A+ breast cancer patients have an increased prevalence of CD8 T cells specific for these novel MAM-A epitopes, and vaccination with a MAM-A DNA vaccine significantly increases the number of these CD8 T cells. The identification and translational validation of novel MAM-A epitopes has important implications for the ongoing clinical development of vaccine strategies targeting MAM-A. The novel MAM-A epitopes represent attractive targets for epitope-based vaccination strategies, and can also be used to monitor immune responses. Taken together these studies provide additional support for MAM-A as an important therapeutic target for the prevention and treatment of breast cancer.

Original languageEnglish
Pages (from-to)527-537
Number of pages11
JournalBreast Cancer Research and Treatment
Volume147
Issue number3
DOIs
StatePublished - Sep 24 2014

Keywords

  • Cancer vaccine
  • Immune therapy
  • Mammaglobin A
  • T cell epitopes

Fingerprint Dive into the research topics of 'Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes'. Together they form a unique fingerprint.

Cite this