Induction of Tumor-specific Cytotoxic Tlymphocytes from Regional Lymph Node Lymphocytes of Human Breast Cancer

人乳腺癌区域淋巴结淋巴细胞诱导肿瘤特异性细胞毒性T淋巴细胞

• 批准号: 09671269
• 负责人: YOSHINO Ichiro
• 金额: $ 1.6万
• 依托单位: University of Occupational and Environmental Health
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 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-09671269/
• 关键词: Breast cancer; Cytotoxic T lymphocyte; Regional lymph node lymphocyte; HLA-A2; Tumor antigen; Major histocompatibility antigen; 主要組織適合抗原; 細胞障害性T細胞; 癌抗原

In this study, we have induced the breast cancer-specific cytotoxic T lymphocytes (CTL) from regional lymph node lymphocytes (RLNL) of HLA A2-positive patients with breast cancer. Freshly isolated RLNL were stimulated with solid phase anti-CD3 monoclonal antibody followed by expansion with recombinant interleukin-2. Subsequently, the RLNL were stimulated with an irradiated HLA 0201 breast cancer cell line, MCF-7, at responder/stimulator ratio of 10/1 once a week for 2 weeks. The cultured RLNL exhibited specific lysis against MCF-7 in all 5 HLA A2-positive patients tested, but not in 2 HLA A2-negative patients. The cytotoxicity against MCF-7 was substantially inhibited by an addition of anti-HLA A2 mAb. In 3 out of the 5 HLA A2-positive patients, the anti-MCF-7 CTL also exhibited a substantial level of reactivity against PC-9, an HLA A0206-positive lung adenocarcinoma cell line. Inversely, anti-PC-9-speciflc CTL was inducible by multiple stimulations of the RLNL with PC-9 cells in 2 out of the 3 patients. These results suggested that several common tumor antigens might exist among HLA A2-positive breast cancers, some of which may be shared with lung adenocarcinomas.

在这项研究中，我们从HLA - a2阳性乳腺癌患者的区域淋巴结淋巴细胞（RLNL）中诱导乳腺癌特异性细胞毒性T淋巴细胞（CTL）。用固相抗cd3单克隆抗体刺激新分离的RLNL，然后用重组白细胞介素-2扩增。随后，用辐照过的HLA 0201乳腺癌细胞系MCF-7，以10/1的应答器/刺激器比例刺激RLNL，每周1次，持续2周。培养的RLNL在所有5例HLA - a2阳性患者中表现出对MCF-7的特异性裂解，但在2例HLA - a2阴性患者中没有。添加抗hla A2单抗后，MCF-7的细胞毒性被显著抑制。在5例HLA - a2阳性患者中的3例中，抗mcf -7 CTL对HLA - a0206阳性肺腺癌细胞株PC-9也表现出相当水平的反应性。相反，在3名患者中，2名患者通过PC-9细胞对RLNL的多次刺激诱导出了抗PC-9特异性CTL。这些结果提示，在HLA - a2阳性乳腺癌中可能存在几种常见的肿瘤抗原，其中一些抗原可能与肺腺癌共有。

项目成果

Yoshino et al.: "The induction of cytotoxic T lymphocytes against HLA-A locus-matched long adenocarclnema in patlents with mon-small ceil lung cancer" Japanese Journal of Cancer Research. 88. 743-749 (1997)

Yoshino 等人：“针对单小细胞肺癌患者中 HLA-A 位点匹配的长腺癌诱导细胞毒性 T 淋巴细胞”，日本癌症研究杂志。

Yoshino et al.: "Postoperative plognosis in patiients with mon-small ceil lung cancer with synchronous intrapulmencry metastases" Annals of Thoracic Surgery. 64. 809-813 (1997)

Yoshino 等人：“伴有同步肺内转移的单小细胞肺癌患者的术后预后”《胸外科年鉴》。

Ryozo Eifuku: "Induction of Tumor-specific Cytotoxic Tlymphocytes from Regional Lymph Node Lymphocytes of Human Breast Cancer" Breast cancer. 5. 367-373 (1998)

Ryozo Eifuku：“从人类乳腺癌区域淋巴结淋巴细胞中诱导肿瘤特异性细胞毒性 T 淋巴细胞”乳腺癌。

Yoshimatsu et al.: "Expression of melanoma antigen-encoding gene in human lung cancer" Journal of Surgical Ohcology. 67. 126-129 (1998)

Yoshimatsu 等人：“黑色素瘤抗原编码基因在人类肺癌中的表达”《外科肿瘤学杂志》。

Ryozo Eifuku, Ichiro Yoshino, et al.: "Induction of Tumor-specific Cytotoxic T lymphocytes from Regional Lymph Node Lymphocytes of Human Breast Cancer" Brerast cancer. 5. 367-373 (1998)

Ryozo Eifuku、Ichiro Yoshino 等人：“从人乳腺癌区域淋巴结淋巴细胞中诱导肿瘤特异性细胞毒性 T 淋巴细胞”乳腺癌。