Immune responses in patients with cervical cancer using human papillomavirus (HPV) 16 E7 peptides and autologous dendritic cells

使用人乳头瘤病毒 (HPV) 16 E7 肽和自体树突状细胞对宫颈癌患者的免疫反应

• 批准号: 14571586
• 负责人: MURAKAMI Masaru
• 金额: $ 2.11万
• 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: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571586/
• 关键词: HPV; Cancer Vaccine; Cervical cancer

HPV is present in virtually all cervical cancers, an estimated 99.7 percent and the oncogenic potential of certain HPV types has been clearly demonstrated. HPV-16 can be detected in approximately 50% of squamous cell carcinoma of the cervix. The E6 and E7 genes of HPV-16 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. HPV-E6 and-E7 are selectively retained and expressed in cervical cancer. Therefore they are attractive targets for the immunotherapy. Most sexually active women are eventually exposed to HPV, but there is no data about potential difference in immune response among healthy women and patients with cervical cancer. We have investigated whether HPV-specific CD8+CTL responses can be induced from the human peripheral blood mononuclear cells (PBMC) of patients and healthy women by in vitro stimulation using an HPV-16 E7 peptide and autologous dendritic cells (DC). This study showed that the frequency of specific CTL response was almost similar for both, suggesting that the ability of immune responses is present in both groups.

HPV几乎存在于所有宫颈癌中，估计占99.7%，某些HPV类型的致癌潜力已得到明确证明。HPV-16可以在大约50%的宫颈鳞状细胞癌中检测到。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蛋白的持续表达已被证明是宫颈癌细胞的生长和致瘤性所必需的。HPV-E6和-E7在宫颈癌中选择性保留和表达。因此，它们是免疫治疗的有吸引力的靶点。大多数性活跃的女性最终都会接触到HPV，但没有关于健康女性和宫颈癌患者之间免疫反应的潜在差异的数据。我们已经研究了是否可以通过使用HPV-16 E7肽和自体树突状细胞（DC）的体外刺激从患者和健康女性的人外周血单核细胞（PBMC）诱导HPV特异性CD 8 +CTL应答。本研究表明，两组的特异性CTL应答频率几乎相似，表明两组都存在免疫应答能力。

项目成果

Masaru Murakami, et al.: "Induction of specific cytotoxic T-lymphocyte (CTL) responses in patients with cervical cancer using an human papilomavixus (HPV)-16 E7 peptide and autologous dendritic cells."Acta Obst Gynec Jpn. 54(2). 566 (2002)

Masaru Murakami 等人：“使用人乳头状瘤病毒 (HPV)-16 E7 肽和自体树突状细胞在宫颈癌患者中诱导特异性细胞毒性 T 淋巴细胞 (CTL) 反应。”Acta Obst Gynec Jpn。

H.Asakura, T.Takeshita, T.Araki(eds): "54^<th> Annual congress of the Japan society of obstetrics & gynecology"Monduzzi Editore S.p.A.. 156 (2002)

H.Asakura、T.Takeshita、T.Araki（编）：“第 54 届日本产科学会年会

村上優 他: "子宮頸癌における複数のHPV-16E7ペプチドを利用した特異的細胞傷害性T細胞(CTL)の誘導"Cancer Science. 94s. 432-432 (2003)

Yu Murakami 等人：“在宫颈癌中使用多种 HPV-16E7 肽诱导特异性细胞毒性 T 细胞 (CTL)”，Cancer Science 94s (2003)。

村上優 他: "子宮頸癌における複数のHPV-16 E7ペプチドを利用した特異的細胞傷害性T細胞(CTL)の誘導"Cancer Science. 94s. 432-432 (2003)

Yu Murakami 等人：“在宫颈癌中使用多种 HPV-16 E7 肽诱导特异性细胞毒性 T 细胞 (CTL)”，Cancer Science 94s (2003)。

Masaru Murakami, et al.: "Induction of specific cytotoxic T-lymphocyte(CTL) responses in patients with cervical cancer using an human papillomavirus(HPV)-16 E7 peptide and autologous dendritic cells"Acta Obst Gynec Jpn. 54. 566-566 (2002)

Masaru Murakami 等人：“使用人乳头瘤病毒 (HPV)-16 E7 肽和自体树突状细胞诱导宫颈癌患者特异性细胞毒性 T 淋巴细胞 (CTL) 反应”Acta Obst Gynec Jpn。