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01-10-2014 | Preclinical Study

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

Authors: 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

Published in: Breast Cancer Research and Treatment | Issue 3/2014

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.

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Title: Identification and translational validation of novel mammaglobin-A CD8 T cell epitopes
Authors: 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
Publication date: 01-10-2014
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2014
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-014-3129-x

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