Helicase antigen (HAGE)‐derived vaccines induce immunity to HAGE and ImmunoBody®‐HAGE DNA vaccine delays the growth and metastasis of HAGE‐expressing tumors in vivo

AbstractThe 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 complementarity‐determining regions engineered to express cytotoxic and helper T‐cell epitopes derived from the cancer antigen of interest. The helicase antigen (HAGE) is a cancer testis antigen, which is expressed in TNBC. Herein, we have identified a 30‐amino‐acid‐long HAGE‐derived sequence containing human leukocyte antigen (HLA)‐A2‐ and HLA‐DR1‐restricted epitopes and demonstrated that the use of this sequence as a peptide (with CpG/incomplete Freund's adjuvant) or incorporated into an ImmunoBody vaccine can generate specific interferon‐γ‐secreting splenocytes in HHDII+DR1+ mice. T‐cell responses elicited by the ImmunoBody‐HAGE vaccine were superior to peptide immunization. Moreover, splenocytes from ImmunoBody‐HAGE‐vaccinated mice stimulated in vitro could recognize HAGE+ tumor cells and the human TNBC cell line MDA‐MB‐231. More importantly, the growth of implanted HHDII+DR1+HAGE+Luc+ B16 cells.