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Identification of genes encoding tumor-rejection antigens of cancers from digestive tract and development of cancer vaccine

消化道癌症肿瘤排斥抗原编码基因的鉴定及癌症疫苗的开发

基本信息

批准号：
09470271
负责人：
ITOH Kyogo
金额：
$ 8.13万
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 (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09470271/
关键词：
cancer of digestive tract tumor-rejection antigen gene cloning cancer vaccine HLA-class I SART1 Peptide antigen HLA-クラスI

项目摘要

1) Detection of specific immunity at the tumor sites of digestive tract. One of the fundamental questions in human tumor immunology is whether HLA-class I-restricted and tumor-specific CTLs exist in tumor sites of cancers originated from digestive tract. or not. We have been addressing this question by testing CTL activity of T cells infiltrating into the various cancers of digestive tract after in vitro incubation with interleukin-2. The results showed the presence of HLA-class I-restricted and tumorspecific CTLs at the tumor sites in all the cancer tested, including esophageal cancers, gastric cancers, and colon cancers. For detailed characterization of these CTLs, please see the manuscripts in the peer-reviewed journals that are attached as appendices 1 (CTLs at the sites of esophageal cancers), 2 (CTLs at gastric cancers), and 3 (CtLs at colon cancers)2) Identification of genes encoding tumor-rejection antigens from cancer of digestive tract. The second question in the human tumor … More immunology is whats' molecules are recognized by these CTLs. Four new genes (SART1, SART2, SART3, and SART4) encoding tumor-rejection antigens have been cloned from cDNA library of human esophageal cancer cells. The peptides encoded by these genes are recognized by either HLA-A24 or-A26-restricted CTLs. HLA-A24 or-A26 allele is found in 60 or 22 % of Japanese. Some of these peptides have the strong activity to induce HLA-class I-restricted CTLs capable of lysing tumor cells. Further, antigens encoded by these genes are highly expressed in cancers of digestive tracts, including head and neck cancers, esophageal cancers, gastric cancers, and colorectal cancers. Therefore, these peptides could be available for relatively large number of cancer patients of digestive tract. For the detailed characterization of SART1 gene, please see the manuscripts in the peer-reviewed journals that re attached as appendices 4 (identification of SART1 gene), 5 (induction of CTLs by the SART1 peptides), 6 (SART1 expression in breast cancer), and 7 (SART1 expression in head and neck cancers). The manuscripts on the SART2 and SART3 genes are under submission for the journals, and that on SART4 genes is in preparation. Less

1)消化道肿瘤部位特异性免疫检测。人类肿瘤免疫学的一个基本问题是hla - i类限制性和肿瘤特异性ctl是否存在于消化道肿瘤的肿瘤部位。与否。我们已经通过白细胞介素-2体外培养后浸润到消化道各种癌症的T细胞的CTL活性来解决这个问题。结果显示，在所有测试的癌症（包括食管癌、胃癌和结肠癌）的肿瘤部位都存在hla - i类限制性和肿瘤特异性ctl。有关这些ctl的详细描述，请参阅同行评审期刊的手稿，附件1（食管癌部位的ctl）， 2（胃癌部位的ctl）和3（结肠癌部位的ctl）。2)消化道癌症肿瘤排斥抗原编码基因的鉴定。人类肿瘤的第二个问题，更多的是免疫学，是这些ctl识别什么分子。从人食管癌细胞cDNA文库中克隆了4个新的肿瘤排斥抗原编码基因（SART1、SART2、SART3和SART4）。这些基因编码的肽可被HLA-A24或a26限制性ctl识别。HLA-A24或a26等位基因在60%或22%的日本人中被发现。其中一些肽具有很强的活性，可以诱导能够裂解肿瘤细胞的hla - i类限制性ctl。此外，这些基因编码的抗原在消化道癌症中高度表达，包括头颈癌、食管癌、胃癌和结直肠癌。因此，这些肽可用于相对较多的消化道肿瘤患者。关于SART1基因的详细描述，请参见附录4 （SART1基因的鉴定）、5 （SART1肽诱导ctl）、6 （SART1在乳腺癌中的表达）和7 （SART1在头颈癌中的表达）的同行评议期刊稿件。关于SART2和SART3基因的论文正在投稿中，关于SART4基因的论文正在准备中。少