BASIC RESEARCH FOR TUMOR SPECIFIC IMMUNOTHERAPY USING TUMOR REJECTED ANTIGEN GENES

利用肿瘤排斥抗原基因进行肿瘤特异性免疫治疗的基础研究

• 批准号: 09470253
• 负责人: HARAHGUCHI Masaru
• 金额: $ 7.49万
• 依托单位: KYUSHU UNIVERSITY
• 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-09470253/
• 关键词: tumor rejection antigen; MAGE; tumor specific immunotherapy; peptide; HLA; 腫瘍拒絶抗体; 遺伝子導入; ベクター; 特異的CTL

For the development of immunotherapy using MAGE peptides, the identification of additional tumor antigens is required. Because HLA-A24 is the most common allele in Japanese, MAGE-3 encoded synthetic peptides with binding affinity for HLA-A24 were tested for the induction of specific CTLs from the peripheral blood mononuclear cells (PBMCs) of HLA-A24 healthy donors. The induced CTLs coud lyseHLA-A24 carcinoma cells expressing MAGE-3, as well as the peptidepulsed target cells, in an HLA-class I restricted manner.We evaluated 38 node positive gastric carcionoma patients who underwent surgery. Primary lesions and metastatic lymph nodes of gastric carcinoma were analyzed in paraffin embedded sections using anti-MAGE-3 monoclonal antibody (mAbs). Immunopositive cells of MAGE-3 protein showed cytoplasmic staining and nonmalignant cells within stomach tissues were immunonegative. The expression of MAGE-3 protein was detected in 17 (45%) primary lesions and 12 (32%) metastatic lymph nodes of 38 cases. In most specimens of gastric carcinoma, a heterogeneous pattern of staining was recognized, especially in metastatic lymph nodes.

为了开发使用法师肽的免疫疗法，需要鉴定其他肿瘤抗原。由于HLA-A24是日本人最常见的等位基因，因此测试了法师-3编码的对HLA-A24具有结合亲和力的合成肽用于从HLA-A24健康供体的外周血单个核细胞（PBMC）诱导特异性CTL。诱导的CTL能以HLA-I类限制性方式裂解表达法师-3的HLA-A24癌细胞和肽脉冲的靶细胞。用抗MAGE-3单克隆抗体（mAb）对胃癌原发灶和转移淋巴结进行石蜡包埋切片分析。法师-3蛋白免疫阳性细胞呈胞浆染色，胃组织中的非恶性细胞呈免疫阴性。法师-3蛋白在38例原发灶和转移淋巴结中的表达率分别为45%（17/38）和32%（12/38）。在大多数胃癌标本中，染色的异质性模式是公认的，特别是在转移淋巴结。

项目成果

Sadanaga N,Mori M,Nagashima H,Tahara K,Fujie T,Tanaka F,Akiyoshi T.: "Expression of MAGE genes and possibility of tumor-specific immunotherapy in colorectal carcinoma." Biotech Lab International. 3. 19-21 (1998)

Sadanaga N、Mori M、Nagashima H、Tahara K、Fujie T、Tanaka F、Akiyoshi T.：“结直肠癌中 MAGE 基因的表达和肿瘤特异性免疫治疗的可能性。”

Haraguchi M: "Expression spectrum of MAGE gene family members in colorectal carcinoma." Arch Pathol Lab Med. 122. 551-554 (1998)

Haraguchi M：“结直肠癌中 MAGE 基因家族成员的表达谱。”

Haraguchi,M: "Motility related protein 1 (MRP1/CD9) expression in colon cancer" clin cancer Res. 4. 1507-1510 (1998)

Haraguchi,M：“结肠癌中运动相关蛋白 1 (MRP1/CD9) 的表达”临床癌症研究。