Petcutaneats Peptide immuni Eation Via Lorneum tarrier-disrupted murine skin for fumorimmunoprophylaxis.

Petcutaneats 肽免疫通过 Lorneum tarrier 破坏的小鼠皮肤进行摄入，用于 Fumorimmuno 预防。

• 批准号: 10470187
• 负责人: TAKIGAWA Masahiro
• 金额: $ 7.62万
• 依托单位: Hamumatsu University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10470187/
• 关键词: CTL; fumor cell; Langerhans cell; barrier-disruption; tape-stripping; 腫瘍抗原ペプチド; 腫瘍免疫; ワクチン; 抗原ペプチド; 皮膚; 角質層; バリア破壊; 癌抗原ペプチド; 癌免疫治療; 癌ワクチン

H-2K^b-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 la^<b+> 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.

H-2K^B限制的肿瘤表位肽，包括酪氨酸酶相关的蛋白2残基181-188（TRP-2）和连接蛋白37残基52-59（MUT1），用于渗透性屏障屏障中断的C57BL/6（b6）的C57BL/6（B6），这些c57BL/6（B6）通过tapitum corneum cortavip tabite cortip tabite cortip tabite tapite cortimis cortimis cortimis cortimis cortimis corter corter corter corter corter corter cover corter corter corter corter corter corter taper。该过程在淋巴结和脾脏中引发的肿瘤特异性细胞毒性T淋巴细胞（CTL），保护小鼠免受相应的肿瘤细胞的随后挑战，并抑制了已建立的肿瘤的生长。预防和治疗有效性与肿瘤特异性CTL前体的频率相关。与完整皮肤的MHC II类LA^<B+>细胞相比，与皮肤的皮肤分离出来，CTL表现出强大的抗原呈递能力，这表明肽施用后的CTL膨胀主要由表皮Langerhans细胞介导。因此，通过屏障干扰的皮肤免疫经皮肽免疫提供了一种简单且无创的手段，可诱导有效的抗肿瘤免疫，可用于癌症免疫疗法。

项目成果

Seo N., Tokura Y., Takigawa M., Egawa K.: "Depletion of IL-10 and TGF-β-producing regulatory γδ T cells by administering a daunomycin-conjugated specific monoclonal antibody in early tumor lesions augments the activity of CTLs and NK cells"Jounral of Immu

Seo N.、Tokura Y.、Takikawa M.、Ekawa K.：“通过在早期肿瘤病变中施用道诺霉素缀合的特异性单克隆抗体来消除产生 IL-10 和 TGF-β 的调节性 γδ T 细胞，从而增强 CTL 的活性和NK细胞“免疫学杂志”

Ohshima A. 他3名: "Formation of Antigenic quinolone photoadducts on langerhans cells initiates photoallergy to systemically administered quinolone in mice."Journal of Investigative Dermatology. 114. 569-575 (2000)

Ohshima A. 和其他 3 人：“朗格汉斯细胞上抗原喹诺酮光加合物的形成引发小鼠对全身施用喹诺酮的光过敏。”研究皮肤病学杂志 114. 569-575 (2000)。

Tokura Y., Yagi H., Seo N., Takagi T., Takigawa M.: "Nonerythrodermic, leukemic variant of cutaneous T-cell lymphoma with indolent clinical course : Th2-type tumor cells lacking T-cell receptor/CD3 expression and coinfiltrating tumoricidal CD8+ T cells."J

Tokura Y.、Yagi H.、Seo N.、Takagi T.、Takikawa M.：“皮肤 T 细胞淋巴瘤的非红皮病、白血病变异，具有惰性临床过程：Th2 型肿瘤细胞缺乏 T 细胞受体/CD3 表达和

Y.Tokura: "Cross-reactivity in murine fluoroquinolene photoallery exclusive usage of vb13 by tommunoe T cells that recognize fluoroquindme-photo modifid cells" J.Immunol. 160. 3719-3728 (1998)

Y.Tokura：“识别氟喹啉-光修饰细胞的 tommunoe T 细胞仅使用 vb13 导致小鼠氟喹啉光敏反应中的交叉反应”J.Immunol。

Takigawa M. 他1名: "Percutaneous peptide immunization via corneum barrier-disrupted murine skin for experimental"Ann.NY Acad.Sci.. (in press). (2001)

Takikawa M. 和其他 1 人：“通过角质屏障破坏的小鼠皮肤进行经皮肽免疫进行实验”Ann.NY Acad.Sci.（出版中）。