Establishment of tumor specific killer T-cells and the cloning of the tumor rejection antigen gene

肿瘤特异性杀伤T细胞的建立及肿瘤排斥抗原基因的克隆

• 批准号: 08671499
• 负责人: YAMANA Hideaki
• 金额: $ 1.47万
• 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: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1997
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08671499/
• 关键词: Esophageal cancer.; Cancer-specific immunity.; Cytotoxic Tlymphocytes.; Tumor-rejection antigens.; Gene cloning.; Antigenic peptides.; Metastatic lymph nodes.; Cancer vaccine.

We in vestigated the presence of HLA-class I-restricted and tumor-specific CTL in tumor sites of esophageal can cers. HLA-class I-restricted and tumor-specific CTL lines were established from metastatic sites in 5 of 15 patients (Toh et. al., Cell. Immunol. 177 : 137-143,1997). In contrast to these five cases, there was no TIL proliferation in any of four cases of metastatic LN that had undergone prepperative chemotherapy and/or radiation or in six cases of original esophageal tumors. CTL were not generated from lymphocytes of non-metastatic region al LN in any of five patients. These results suggest the existence of HLA-class I-restricted and tumor-specific CTL in tumor sites of esophageal SCC patients who had no preoperative chemotherapy and/or radiation.We have identified a gene encoding tumor antigens from cDNA library of esophageal squamous cell carcinomas (SCCs) recognizes by HLA-A2601-restricted CTLs (Shichijo et al., J.Exp. Med. 187 : 277-288,1998). This gene showed no similarity to known sequences, and encoded two (125 and 43 kD) proteins. The 125 kD protein with leucine-zipper motif was expressed in the nucleus of the majority of proliferating cells tested including normal and malignant cells. The 43 kD protein was expressed in the cytosol of most of SCCs from various organs and half of lung adenocarcinomas, but was not expressed in other cancers nor in a panel of normal tissues. The three nonapeptides in the region shared by the two proteins were recognized by the KE4 CTLs, and one of the peptides induced in vitro from PBMCs the CTLs restricted to the autologous tumor cells. The 43 kD protein and this nonapeptide (KGSGKMKTE) may be useful for specific immunotherapy of HLA-A2601^+ epithelial cancer patients.

我们研究了食管癌肿瘤部位hla - i类限制性和肿瘤特异性CTL的存在。15例患者中有5例从转移部位建立了hla - i类限制性和肿瘤特异性CTL系(Toh等人，Cell。免疫学杂志。177:137-143,1997)。与这5例相比，4例接受化疗和/或放疗的转移性LN患者和6例原发食管肿瘤患者均未见TIL增生。5例患者的非转移区淋巴细胞均未产生CTL。这些结果表明，在术前未接受化疗和/或放疗的食管鳞状细胞癌患者的肿瘤部位存在hla - i类限制性和肿瘤特异性CTL。我们从hla - a2601限制性ctl识别的食管鳞状细胞癌（SCCs） cDNA文库中发现了一个编码肿瘤抗原的基因（Shichijo et al.， J.Exp.）。医学杂志。187:277-288,1998)。该基因与已知序列无相似性，编码两个（125和43 kD）蛋白。具有亮氨酸-拉链基序的125 kD蛋白在大多数增殖细胞（包括正常细胞和恶性细胞）的细胞核中表达。43 kD蛋白在大多数来自各种器官的SCCs和一半的肺腺癌的细胞质中表达，但在其他癌症和一组正常组织中未表达。这两种蛋白共享区域的三个非肽被KE4 ctl识别，其中一个肽从pbmc体外诱导的ctl限制在自体肿瘤细胞中。43 kD蛋白及其非肽（KGSGKMKTE）可能对HLA-A2601^+上皮癌患者的特异性免疫治疗有用。

项目成果

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Toh,Y.,Itoh,K.等人：“食管癌 MAGE-1 基因的表达。”

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Chandawarkar RY、Yamana H、Fujitoh H 等人：“用于与食管癌相关的特定淋巴结组的预备分期的内超声检查。”

Chandawarkar, R.Y., et al..: "Endosonography for preoperative staging of specific nodal groups associated with esophageal cancer." World J.Surg.20. 700-702 (1996)

Chandawarkar, R.Y. 等人：“用于与食管癌相关的特定淋巴结组的术前分期的内超声检查。”

Bhansali, M.S., et al.: "Pattern of recurrence after extended radical esophagectomy with three-field lymph node dissection for squamous cell carcinoma in the thoracic esophagus." World J.Surg.21. 275-281 (1997)

Bhansali, M.S. 等人：“胸段食管鳞状细胞癌扩大根治性食管切除术和三野淋巴结清扫术后的复发模式。”

Toh,H.,Itoh,K.,at al.: "A monoclonal antibody KIS-1 recognizing a new membrane antigen on squamous cell carcinoma." Int.J.Cancer,. 66. 600-606 (1996)

Toh,H.,Itoh,K.,at al.：“单克隆抗体 KIS-1 识别鳞状细胞癌上的新膜抗原。”