Induction of HCA587-Specific Antitumor Immunity with HCA587 Protein Formulated with CpG and ISCOM in Mice

HCA587 (also known as MAGE-C2) is a “cancer-testis” antigen highly expressed in a number of malignancies with unique immunological properties, making it a promising target for tumor immunotherapy. In this report, we demonstrated that HCA587 protein, when formulated with adjuvants CpG–containing oligodeoxynucleotides (CpG ODN) and ISCOM, was capable of inducing a potent cellular and humoral immune response as indicated by the presence of a large number of HCA587-specific, IFN-γ-producing CD4+ T cells and high levels of HCA587-specific antibodies. More importantly, vaccination with HCA587 conferred protection against challenge with HCA587-expressing B16 melanoma in prophylactic and therapeutic settings. In analysis of the mechanisms underlying the protective effect, we showed that the vaccination was followed by enhanced accumulation of tumor-infiltrating lymphocytes (TILs) with enrichment of conventional CD4+ T cells but reduced representation of Treg cells. Further, the antitumor effect was largely abrogated in mice either depleted of CD4+ T cells or deficient for IFN-γ. These results indicate that HCA587 protein vaccine possesses evident antitumor activity in a mouse model and holds promise for treatment of human cancers.HCA587（亦称MAGE-C2）是一类癌-睾丸抗原（cancer-testis antigen），在多种恶性肿瘤中呈高表达状态，且具备独特的免疫学特性，使其成为肿瘤免疫治疗极具潜力的靶点。本研究证实，将HCA587蛋白与含CpG基序的寡脱氧核苷酸（CpG ODN）及免疫刺激复合体（ISCOM）佐剂联合配制后，可诱导强烈的细胞免疫与体液免疫应答，具体表现为大量分泌γ干扰素（IFN-γ）的HCA587特异性CD4+ T细胞，以及高滴度的HCA587特异性抗体。更为关键的是，在预防性与治疗性给药场景中，接种HCA587疫苗均可对表达HCA587的B16黑色素瘤细胞攻击产生防护作用。在对该防护效应的潜在机制进行分析后，研究团队发现，接种疫苗后肿瘤浸润淋巴细胞（TILs）的浸润水平显著提升，其中常规CD4+ T细胞发生富集，而调节性T细胞（Treg cells）的占比则出现降低。进一步实验显示，若小鼠体内CD4+ T细胞被耗竭或IFN-γ功能缺陷，其抗肿瘤效应会大幅减弱。上述结果表明，HCA587蛋白疫苗在小鼠模型中展现出明确的抗肿瘤活性，为人类癌症的治疗提供了潜在的应用前景。