IMMUNOTHERAPY OF HUMAN COLON-CANCER BY ANTIBODY-TARGETED SUPERANTIGENS
IMMUNOTHERAPY OF HUMAN COLON-CANCER BY ANTIBODY-TARGETED SUPERANTIGENS
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DOI：
10.1007/bf01521342
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发表时间：
1995-09-01
影响因子：
5.8
通讯作者：
KALLAND, PLT
中科院分区：
文献类型：
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作者：
DOHLSTEN, M;LANDO, PA;KALLAND, PLT
T 淋巴细胞通常无法识别人类结肠癌，这表明该肿瘤超出了免疫治疗的范围。细菌超抗原是已知最有效的人类 T 淋巴细胞激活剂，可诱导 T 细胞的细胞毒性和细胞因子的产生。为了开发基于 T 细胞的结肠癌疗法，超抗原葡萄球菌肠毒素 A (SEA) 通过与与人类结肠癌发生反应的单克隆抗体 C242 的 Fab 片段进行基因融合，从而具有肿瘤反应性。 C242Fab-SEA 融合蛋白在体外以纳摩尔浓度靶向 SEA 反应性 T 细胞对抗 MHC II 类阴性人类结肠癌细胞。对人源化 SCLD 小鼠体内生长的播散性人类结肠癌进行治疗，可显着抑制肿瘤生长，并明显治愈动物。治疗效率取决于融合蛋白和人类 T 细胞的肿瘤特异性。免疫组织化学证明 C242Fab-SEA 处理的肿瘤中存在大量人类 T 细胞浸润。该结果值得进一步评估 C242Fab-SEA 融合蛋白作为结肠癌患者的免疫疗法，
T lymphocytes generally fail to recognize human colon carcinomas, suggesting that the tumour is beyond reach of immunotherapy. Bacterial superantigens are the most potent known activators of human T lymphocytes and induce T cell cytotoxicity and cytokine production. In order to develop a T-cell-based therapy for colon cancer, the superantigen staphylococcal enterotoxin A (SEA) was given tumour reactivity by genetic fusion with a Fab fragment of the monoclonal antibody C242 reacting with human colon carcinomas. The C242Fab-SEA fusion protein targeted SEA-reactive T cells against MHC-class-II-negative human colon carcinoma cells in vitro at nanomolar concentrations. Treatment of disseminated human colon carcinomas growing in humanized SCLD mice resulted in marked inhibition of tumour growth and the apparent cure of the animals. Therapeutic efficiency was dependent on the tumour specificity of the fusion protein and human T cells. Immunohistochemistry demonstrated massive infiltration of human T cells in C242Fab-SEA-treated tumours. The results merit further evaluation of C242Fab-SEA fusion proteins as immunotherapy in patients suffering from colon carcinoma,