The management of patients with triple-negative breast cancer (TNBC) continues to pose a significant clinical challenge. Less than 30% of women with metastatic TNBC survive 5 years, despite adjuvant chemotherapy and the initial higher rates of clinical response that can be achieved with neoadjuvant chemotherapy. ImmunoBody? is a plasmid DNA designed to encode a human antibody molecule with complementary determining regions (CDRs) engineered to express cytotoxic and helper T cell epitopes derived from the cancer antigen of interest. HAGE is a Cancer Testis Antigen, which is expressed in TNBC. Herein, we have identified a 30-amino-acid-long HAGE-derived sequence containing HLA-A2 and HLA-DR1 restricted epitopes ... More
The management of patients with triple-negative breast cancer (TNBC) continues to pose a significant clinical challenge. Less than 30% of women with metastatic TNBC survive 5 years, despite adjuvant chemotherapy and the initial higher rates of clinical response that can be achieved with neoadjuvant chemotherapy. ImmunoBody? is a plasmid DNA designed to encode a human antibody molecule with complementary determining regions (CDRs) engineered to express cytotoxic and helper T cell epitopes derived from the cancer antigen of interest. HAGE is a Cancer Testis Antigen, which is expressed in TNBC. Herein, we have identified a 30-amino-acid-long HAGE-derived sequence containing HLA-A2 and HLA-DR1 restricted epitopes and demonstrated that the use of this sequence as peptide (with CpG/IFA) or incorporated into an ImmunoBody? vaccine can generate specific IFNγ secreting splenocytes in HHDII/DR1 mice. T-cell responses elicited by the ImmunoBody?-HAGE vaccine were superior to peptide immunisation. Moreover, splenocytes from ImmunoBody?-HAGE vaccinated mice stimulated in vitro could recognise HAGE tumour cells and the human TNBC cell line MDA-MB-231. More importantly, the growth of implanted B16/HHDII/DR1/HAGE cells was significantly delayed by the ImmunoBody?-HAGE vaccine in both prophylactic and experimental metastasis settings. Overall, we demonstrate the potential of HAGE-derived vaccines for treating HAGE-expressing cancers and that such vaccines could be considered as therapeutic options for patients with HAGE TNBC after conventional treatment to prevent disease recurrence.
