Specific immunotherapy for cervical cancer by using human papillomavirus protein and dendritic cells

人乳头瘤病毒蛋白和树突状细胞对宫颈癌的特异性免疫治疗

• 批准号: 11671652
• 负责人: MURAKAMI Masaru
• 金额: $ 0.9万
• 依托单位: Tokai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671652/
• 关键词: HPV; Immunotherapy for cancer; Peptide therapy; Cervical Cancer; Cancer Vaccine

Cervical cancer is one of the most common causes of cancer-related death in women. As a result of several recent advantages in molecular biology, Human papillomavirus (HPV) is present in virtually all cervical cancers, an estimated 99.7 percent.. The E6 and E7 genes of HPV-l6 encode for oncoproteins that can immortalize human keratinocytes. Continued expression of the E6 and E7 proteins has been shown to be necessary for the growth and tumorigenicity of cervical carcinoma cells. Therefore they are attractive targets for the immunotherapy. But several studies have shown that peptides alone are not very efficient in inducing cytotoxic T lymphocytes (CTL) responses both in vitro and in vivo, and that immune adjuvants may play an important role. Among adjuvants, dendritic cells (DC) appear to play a critical role on antigen presentation in vivo and initiate immune responses. In this study, autologous DC co-cultured with a recombinant HPV-16 E6/E7 fusion protein could successfully induce specific CTL.This result suggests that DC may be capable of engulfing extracellular viral protein, which can then undergo intracellular processing in the class I pathway to permit the peptide fragments to become available for CTL.

宫颈癌是女性癌症相关死亡的最常见原因之一。由于最近在分子生物学方面的一些优势，人乳头瘤病毒(HPV)在几乎所有宫颈癌中都存在，估计有99.7%。HPV-16的E6和E7基因编码可使人角质形成细胞永生化的癌蛋白。E6和E7蛋白的持续表达对宫颈癌细胞的生长和致瘤性是必要的。因此，它们是免疫治疗的有吸引力的靶点。但一些研究表明，在体外和体内，单靠多肽诱导细胞毒性T淋巴细胞(CTL)反应并不是很有效，免疫佐剂可能起到重要作用。在佐剂中，树突状细胞(DC)似乎在体内抗原提呈和启动免疫反应中起着关键作用。在本研究中，自体树突状细胞与重组HPV-16E6/E7融合蛋白共培养可成功诱导出特异性CTL，这一结果提示DC可能能够吞噬细胞外病毒蛋白，然后在I类途径中进行细胞内处理，使多肽片段可用于CTL。

项目成果

Joseph Monsonego: "4^<th>International Multidisciplinary Congress Eurogin 2000"Monduzzi Editore S.p.A.. 5 (2000)

Joseph Monsonego：“4^<th>国际多学科大会 Eurogin 2000”Monduzzi Editore S.p.A.. 5 (2000)

村上優: "樹状細胞とHuman papillomavirus-16 E7ペプチドを利用した特異的細胞障害性T細胞の誘導"日本産婦人科学会誌. 51巻. S288 (1999)

Masaru Murakami：“使用树突状细胞和人乳头瘤病毒 16 E7 肽诱导特异性细胞毒性 T 细胞”，日本妇产科学会杂志，第 51 卷，S288（1999 年）。

Murakami M, et al.: "Autologous dendritic cells with an human papillomavirus-16 E6/E7 fusion protein for the induction of specific cellular immune response, in Joseph Monsonego (eds) : 4^<th> International Multidisciplinary Congress Eurogin 2000"Monduzzi

Murakami M 等人：“自体树突状细胞与人乳头瘤病毒 16 E6/E7 融合蛋白用于诱导特异性细胞免疫反应，Joseph Monsonego（编辑）：第 4 届国际多学科大会 Eurogin 2000”Monduzzi

Murakami M, et al.: "Induction of specific cytotoxic T-lymphocyte responses using an HPV-16 E7 peptides and dendritic cells."Acta Obst Gynaec JPN. vol.51. s288 (1999)

Murakami M 等人：“使用 HPV-16 E7 肽和树突状细胞诱导特异性细胞毒性 T 淋巴细胞应答。”Acta Obst Gynaec JPN。

Murakami Masaru: "Induction of specific CD8+ T-lymphocyte responses using a human papillomavirus-16 E6/E7 fusion protein and autologous dendritic cells"Cancer Research. 59. 1184-1187 (1999)

Murakami Masaru：“使用人乳头瘤病毒 16 E6/E7 融合蛋白和自体树突状细胞诱导特异性 CD8 T 淋巴细胞反应”癌症研究。