Basic study of tumor-vaccine for metastatic epithelial cancer.

转移性上皮癌肿瘤疫苗的基础研究。

• 批准号: 12670533
• 负责人: SHICHIJO Shigeki
• 金额: $ 2.05万
• 依托单位: Kurume University school of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670533/
• 关键词: Tumor rejection antigen; Metastasis; Epithelial cancer; lck; Peptide antigen; Cytotoxic T cell; aberrantly expression; promotor; 食道癌

A lck gene was identified by the gene-expression cloning method, in which a KE4-cytotoxic T cell (CTL) line was used. The KE4-CTL line was previously established from tumor-infiltrating lymphocytes (TILs) of squamous cell carcinoma. The Lck protein (p56k/c), a src family tyrosine kinase which is essential for T cell development and function, is aberrantly expressed in metastatic colon cancers. The type I transcript was used in the cancer cell lines, in agreement with the results reported previously, whereas the type II transcript was used in normal cells and tissues.Further, all p56^<lck> esophageal cancer cell lines were established from the primary esophageal tumors patients who had distinct metastases, including the KE4 tumor cells from which the lck gene was cloned as a gene encoding tumor-rejection antigen. p56^<lck> seems to facilitate the malignant transformation of epithelial cells through initiation of anchorage-independent proliferation. We identified three peptides (Lck208-216, Lck486-494, and Lck488-497), which were recognized by KE4-CTL. These Lck peptides augmented CTh activity in peripheral blood mononuclear cells of colon and other epithelial cancer patients with metastasis, but not those without metastasis. CTL precursors recognizing the Lck peptide were identified in freshly prepared PBMCs of metastatic cancer patients, and their frequency was significantly augmented by the stimulation with the peptide. Thus, Lck peptides could be useful for specific immunotherapy toward metastatic cancer patients.

通过基因表达克隆方法鉴定lck基因，其中使用KE 4-细胞毒性T细胞（CTL）系。KE 4-CTL细胞系以前是从鳞状细胞癌的肿瘤浸润淋巴细胞（TIL）中建立的。Lck蛋白（p56 k/c）是一种src家族酪氨酸激酶，对T细胞的发育和功能至关重要，在转移性结肠癌中异常表达。此外，所有p56 ~+<lck>食管癌细胞系均来自具有明显转移的原发性食管肿瘤患者，包括克隆lck基因作为编码肿瘤排斥抗原的基因的KE 4肿瘤细胞。p56 α<lck>似乎通过启动锚定非依赖性增殖促进上皮细胞的恶性转化。我们鉴定了三种肽（Lck 208 -216、Lck 486 -494和Lck 488 -497），它们被KE 4-CTL识别。这些Lck肽增强了结肠癌和其他上皮癌转移患者外周血单个核细胞中CTh的活性，但对那些没有转移的患者没有增强作用。识别Lck肽的CTL前体在转移性癌症患者的新鲜制备的PBMC中被鉴定，并且它们的频率通过用肽刺激而显著增加。因此，Lck肽可用于针对转移性癌症患者的特异性免疫疗法。

项目成果

Nanae Harashima: "Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes of cancer patients with distant metastases"European Journal of Immunology. 31. 323-332 (2001)

Nanae Harashima：“具有远处转移的癌症患者的细胞毒性 T 淋巴细胞将 Lck 酪氨酸激酶识别为肿瘤抗原”《欧洲免疫学杂志》。

Harashima N, Tanaka K, Sasatomi T, Shimizu K, Miyagi Y, YamadaA, TamuraA, Yamana H, Itoh K, and Shichiio S: "Recognition of the Lck tyrosine kinase as a tumor antigen by cytotoxic T lymphocytes cancer patients with distant metastases."Eur. J Immunol.. 31.

Harashima N、Tanaka K、Sasatomi T、Shimizu K、Miyagi Y、YamadaA、TamuraA、Yamana H、Itoh K 和 Shichiio S：“具有远处转移的细胞毒性 T 淋巴细胞将 Lck 酪氨酸激酶识别为肿瘤抗原。

Yutani S, Shichiio S. Inoue Y, Kawagoe N, Okuda K, Kurohiji T, Tanaka M, Sata M, and Itoh K: "Expression of the SART 1 tumor-rejection antigen in hepatpcellular carcinomas."Oncol. Report. 8. 369-372 (2001)

Yutani S、Shichiio S. Inoue Y、Kawagoe N、Okuda K、Kurohiji T、Tanaka M、Sata M 和 Itoh K：“肝细胞癌中 SART 1 肿瘤排斥抗原的表达。”Oncol。

Kawagoe N,: "Induction of HLA-class I-restricted and tumor specific CTLs by SART3-derived peptides in patients with renal cell carcinoma."J.Urology,. (in press). (2000)

Kawagoe N，：“SART3 衍生肽在肾细胞癌患者中诱导 HLA-I 类限制性和肿瘤特异性 CTL。”J.Urology，。

Murayana K: "Expression of the SART3 tumor-rejection antigen in brain tumors and induction of cytotoxic T lymphocytes by its peptides"Journal of Immunotherapy. 23. 511-518 (2000)

Murayana K：“脑肿瘤中 SART3 肿瘤排斥抗原的表达及其肽诱导细胞毒性 T 淋巴细胞”免疫治疗杂志。