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 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.

中文翻译：

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解旋酶抗原 (HAGE) 衍生的疫苗诱导对 HAGE 的免疫力，ImmunoBody®-HAGE DNA 疫苗可延迟体内表达 HAGE 的肿瘤的生长和转移

三阴性乳腺癌 (TNBC) 患者的管理继续构成重大的临床挑战。尽管接受了辅助化疗并且新辅助化疗可以达到初始较高的临床反应率，但只有不到 30% 的转移性 TNBC 女性能存活 5 年。ImmunoBody 是一种质粒 DNA，设计用于编码具有互补决定区的人抗体分子，该分子经过工程改造以表达源自目标癌症抗原的细胞毒性和辅助性 T 细胞表位。解旋酶抗原 (HAGE) 是一种癌症睾丸抗原，在 TNBC 中表达。在此，我们确定了一个包含人类白细胞抗原 (HLA)-A2-和 HLA-DR1-限制性表位的 30 个氨基酸长的 HAGE 衍生序列，并证明了将该序列用作肽（具有 CpG/不完全弗罗因德⁺ DR1 ⁺小鼠。ImmunoBody-HAGE 疫苗引发的 T 细胞反应优于肽免疫。此外，体外刺激的免疫身体-HAGE 疫苗接种小鼠的脾细胞可以识别 HAGE ⁺肿瘤细胞和人 TNBC 细胞系 MDA-MB-231。更重要的是，植入的 HHDII ⁺ DR1 ⁺ HAGE ⁺ Luc ⁺ B16 细胞的生长。