首页> 美国卫生研究院文献>Proceedings of the National Academy of Sciences of the United States of America >Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis
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Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental tumor immunoprophylaxis

机译:通过角质层屏障破坏的小鼠皮肤经皮肽免疫以预防肿瘤

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摘要

H-2Kb-restricted tumor epitope peptides, including tyrosinase-related protein 2 residues 181–188 (TRP-2) and connexin 37 residues 52–59 (MUT1), were applied to permeability barrier-disrupted C57BL/6 (B6) mouse skin from which the stratum corneum of the epidermis had been removed by tape-stripping. This procedure primed tumor-specific cytotoxic T lymphocytes (CTLs) in the lymph nodes and spleen, protected mice against subsequent challenge with corresponding tumor cells, and suppressed the growth of established tumors. Preventive and therapeutic effectiveness was correlated with the frequency of tumor-specific CTL precursors. MHC class II Iab+ cells separated from tape-stripped skin, compared with those from intact skin, exhibited a strong antigen-presenting capacity for CTL, suggesting that CTL expansion after peptide application is primarily mediated by epidermal Langerhans cells. Thus, percutaneous peptide immunization via barrier-disrupted skin provides a simple and noninvasive means of inducing potent anti-tumor immunity which may be exploited for cancer immunotherapy.
机译:H-2K b 限制的肿瘤抗原决定簇肽,包括酪氨酸酶相关蛋白2残基181–188(TRP-2)和连接蛋白37残基52–59(MUT1),被用于破坏通透性的屏障C57BL / 6(B6)小鼠皮肤,已通过胶带剥离去除了表皮的角质层。该程序可引发淋巴结和脾脏中的肿瘤特异性细胞毒性T淋巴细胞(CTL),保护小鼠免受随后受到相应肿瘤细胞的攻击,并抑制已建立肿瘤的生长。预防和治疗效果与肿瘤特异性CTL前体的发生频率相关。从胶带剥离的皮肤分离的MHC IIa Ia b + 细胞与从完整皮肤分离的MHC Ia b + 细胞相比,对CTL表现出很强的抗原呈递能力,这表明在肽应用后CTL扩展主要是由表皮朗格汉斯介导细胞。因此,经由破坏屏障的皮肤进行的经皮肽免疫提供了诱导有效的抗肿瘤免疫的简单且非侵入性的方法,其可用于癌症免疫治疗。

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