6P - Investigation of the Helicase Antigen (HAGE) as immunotherapeutic target for breast cancer therapy

Date 21 November 2014
Event ESMO Symposium on Immuno-Oncology 2014
Session Welcome reception and Poster viewing
Topics Breast Cancer
Cancer Immunology and Immunotherapy
Translational Research
Presenter Divya Nagarajan
Authors D. Nagarajan, G. Pockley, R. Rees, S. Mc Ardle
  • School Of Science And Technology, Nottingham Trent University, NG118NS - Nottingham/UK

Abstract

Body

Background: The delivery of specific immunotherapies for malignant tumours requires the identification of relevant tumour antigens and sequences from these which can be used to stimulate protective T cell-mediated immunity. HAGE (DDX43) is a cancer testis antigen belonging to the DEAD box family of helicases found by our group to be over-expressed in many solid cancers including breast cancer (Mathieu et al.1) immunogenic (Mathieu et al.2 and to be a biomarker for poor prognosis as well as a predictor of chemotherapy response in breast cancer (Abdel-fatah et al.3). We propose that HAGE might be a novel immunotherapeutic target for patients bearing breast cancers expressing this antigen. The aim of this study is to identify strongly immunogenic HAGE-derived sequences which can be used for the development of a therapeutic vaccine for HAGE positive cancer.

Experimental Design: The HAGE-derived sequences were identified and assessed after: (i) using a computer-based epitope predictive tool; (ii) determining the affinity of the predicted peptide with HLA-A2.1 molecules using a peptide-binding assay; (iii) confirming the natural endogenous processing of identified peptides using humanised HHDII/DR1 transgenic mice expressing HLA-A2 and HLA-DR1 molecules but no murine Class-I or Class-II molecules.

Results: Two HAGE-derived sequences (a 24 amino acids long and a 30 amino acids long) encompassing several immunogenic epitopes and exhibiting a broad HLA binding spectrum have been identified and their immunogenicity assessed.

Conclusions: The cancer restricted and elevated expression of HAGE in several cancers makes this particular antigen a promising molecule on which to base the development of new T cell-based immunotherapeutic strategies. The novel HAGE-derived sequences identified here might therefore facilitate the development of long peptide-based, broadly applicable cancer vaccines.

References:
1Cancer Immun. 2010 Jan 11;10:2.,
2Cancer Immunol Immunother. 2007 Dec; 56(12):1885-95. Epub 2007 May 9.,
3Br J Cancer. 2014 May 13;110(10):2450-61. doi: 10.1038/bjc.2014.168. Epub 2014 Apr 22.