Antitumor Humoral and T Cell Responses by Mucin-1 Conjugates of Bacteriophage Qβ in Wild-type Mice.

Antitumor Humoral and T Cell Responses by Mucin-1 Conjugates of Bacteriophage Qβ in Wild-type Mice.
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DOI:
10.1021/acschembio.8b00313
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发表时间:
2018-06-15
影响因子:
4
通讯作者:
Huang X
Huang X
中科院分区:
生物学2区
文献类型:
--
作者:
Yin Z;Wu X;Kaczanowska K;Sungsuwan S;Comellas Aragones M;Pett C;Yu J;Baniel C;Westerlind U;Finn MG;Huang X

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Mucin-1 (MUC1) 是排名最高的肿瘤相关抗原之一。为了产生有效的抗 MUC1 免疫反应作为潜在的抗癌疫苗,MUC1 肽和糖肽已与噬菌体 Qβ 共价结合。用这些构建体对小鼠进行免疫,产生了高效的抗体反应,IgG 滴度超过 100 万,这是迄今为止报道的最高抗 MUC1 IgG 滴度之一。此外,高IgG抗体水平持续了六个月以上。该构建体还引发了 MUC1 特异性细胞毒性 T 细胞,可以选择性杀死 MUC1 阳性肿瘤细胞。 Qβ-MUC1 缀合物具有强大诱导针对肿瘤细胞的抗体和细胞毒性 T 细胞免疫的独特能力,这预示着该构建体未来将转化为抗癌疫苗。
Mucin-1 (MUC1) is one of the top ranked tumor associated antigens. In order to generate effective anti-MUC1 immune responses as potential anticancer vaccines, MUC1 peptides and glycopeptides have been covalently conjugated to bacteriophage Qβ. Immunization of mice with these constructs led to highly potent antibody responses with IgG titers over one million, which are among the highest anti-MUC1 IgG titers reported to date. Furthermore, the high IgG antibody levels persisted for more than six months. The constructs also elicited MUC1 specific cytotoxic T cells, which can selectively kill MUC1 positive tumor cells. The unique abilities of Qβ-MUC1 conjugates to powerfully induce both antibody and cytotoxic T cell immunity targeting tumor cells bode well for future translation of the constructs as anticancer vaccines.
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