Investigation of the Helicase Antigen (HAGE) as Immunotherapeutic Target for Breast Cancer Therapy

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ABSTRACT 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. Disclosure All authors have declared no conflicts of interest.