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

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，消化道肿瘤的肿瘤部位是否存在HLAI类限制性CTL和肿瘤特异性CTL。或者不去。我们一直在通过检测在体外与IL-2孵育后渗透到各种消化道癌症中的T细胞的CTL活性来解决这个问题。结果显示，在所有被测试的癌症中，包括食道癌、胃癌和结肠癌，肿瘤部位都存在HLAI类限制性和肿瘤特异性CTL。有关这些CTL的详细特征，请参阅作为附录1(食道癌部位的CTL)、2(胃癌的CTL)和3(结肠癌的CTL)的同行评议期刊上的手稿2)消化道癌肿瘤排斥抗原编码基因的鉴定。人类肿瘤…中的第二个问题更多的免疫学是由这些CTL识别的分子。4个编码肿瘤排斥抗原的新基因(SART1、SART2、SART3和SART4)已从人食道癌细胞的cDNA文库中克隆出来。这些基因编码的多肽可被人类白细胞抗原-A24或-A26限制性CTL识别。在60%或22%的日本人中发现了-A24或-A26等位基因。其中一些多肽具有很强的诱导HLAI类限制性CTL的活性，能够溶解肿瘤细胞。此外，这些基因编码的抗原在消化道癌中高度表达，包括头颈癌、食道癌、胃癌和结直肠癌。因此，这些多肽可供较大数量的消化道癌患者使用。有关SART1基因的详细特征，请参阅同行评议期刊上的手稿，分别附在附录4(SART1基因的鉴定)、5(SART1多肽诱导的CTL)、6(SART1在乳腺癌中的表达)和7(SART1在头颈部癌症中的表达)。关于SART2和SART3基因的手稿正在向期刊提交，关于SART4基因的手稿正在准备中。较少

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