Induction of HCA587-specific antitumor immunity with HCA587 protein formulated with CpG and ISCOM in mice.
Induction of HCA587-specific antitumor immunity with HCA587 protein formulated with CpG and ISCOM in mice.
复制标题
用 CpG 和 ISCOM 配制的 HCA587 蛋白在小鼠中诱导 HCA587 特异性抗肿瘤免疫
DOI：
10.1371/journal.pone.0047219
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Yin Y
中科院分区：
文献类型：
--
作者：
Chen J;Zhang L;Wen W;Hao J;Zeng P;Qian X;Zhang Y;Yin Y
HCA587（也称为MAGE-C2）是一种在多种恶性肿瘤中高度表达的“癌睾丸”抗原，具有独特的免疫学特性，是肿瘤免疫治疗的一个有希望的靶点。在本报告中，我们证明了HCA587蛋白，当与含CpG的寡脱氧核苷酸（CpG ODN）和ISCOM佐剂配制时，能够诱导有效的细胞和体液免疫反应，这表明存在大量HCA587特异性的、产生IFN-γ的CD4+ T细胞和高水平的HCA587特异性抗体。更重要的是，接种HCA587疫苗可以在预防和治疗环境中保护患者免受表达HCA587的B16黑色素瘤的攻击。在对保护作用机制的分析中，我们发现接种疫苗后，肿瘤浸润淋巴细胞（til）的积累增强，常规CD4+ T细胞富集，但Treg细胞的表达减少。此外，在CD4+ T细胞缺失或IFN-γ缺失的小鼠中，抗肿瘤作用基本消失。这些结果表明，HCA587蛋白疫苗在小鼠模型中具有明显的抗肿瘤活性，有望用于治疗人类癌症。
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.
登录
查看更多内容
影响因子：
6.2
作者：
Bode C;Zhao G;Steinhagen F;Kinjo T;Klinman DM
通讯作者：
Klinman DM
影响因子：
--
作者：
Jähnisch H;Füssel S;Kiessling A;Wehner R;Zastrow S;Bachmann M;Rieber EP;Wirth MP;Schmitz M
通讯作者：
Schmitz M
影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
影响因子：
4.6
作者：
Li, B;Wang, Y;Chen, W
通讯作者：
Chen, W