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单克隆抗体靶向超抗原介导的T细胞对人结肠癌的杀伤作用

T cell killing of human colon carcinomas by monoclonal-antibody-targeted superantigens.

作者信息

Lando P A, Dohlsten M, Hedlund G, Akerblom E, Kalland T

机构信息

Kabi Pharmacia Therapeutics, Lund, Sweden.

出版信息

Cancer Immunol Immunother. 1993;36(4):223-8. doi: 10.1007/BF01740903.

Abstract

The bacterial superantigen staphylococcal enterotoxin A (SEA) induces T cell activation as well as directing activated T cells to kill major-histocompatibility-complex-class-II-expressing tumours such as freshly prepared leukemia cells. We now report that conjugates of SEA and the colon-carcinoma-reactive mAb C215 mediate T-cell-dependent killing of freshly isolated cells obtained from surgical specimens of human colon carcinomas. Cytotoxicity was observed at nanomolar concentrations of conjugate while no or very low effects were seen with the mAb C215 or SEA alone. Tumour-infiltrating lymphocytes (TIL) did not exert any cytotoxicity against conjugate-treated tumour cells immediately after isolation. In vitro culture of TIL with interleukin-2 and SEA resulted in SEA-mAb-conjugate-dependent killing of freshly isolated tumour cells. This suggests that mAb-SEA conjugates may be of potential use to target T lymphocytes, including TIL, against colon carcinoma cells in vivo.

摘要

细菌超抗原葡萄球菌肠毒素A(SEA)可诱导T细胞活化,并引导活化的T细胞杀死表达主要组织相容性复合体II类分子的肿瘤,如新鲜制备的白血病细胞。我们现在报告,SEA与结肠癌细胞反应性单克隆抗体C215的偶联物介导了对从人类结肠癌手术标本中获得的新鲜分离细胞的T细胞依赖性杀伤。在纳摩尔浓度的偶联物时观察到细胞毒性,而单独的单克隆抗体C215或SEA则没有或只有非常低的效应。肿瘤浸润淋巴细胞(TIL)在分离后立即对经偶联物处理的肿瘤细胞没有任何细胞毒性作用。用白细胞介素-2和SEA对TIL进行体外培养,导致对新鲜分离的肿瘤细胞产生SEA-单克隆抗体偶联物依赖性杀伤。这表明单克隆抗体-SEA偶联物可能在体内靶向T淋巴细胞(包括TIL)对抗结肠癌细胞方面具有潜在用途。

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本文引用的文献

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Lymphokine-activated killer cell induction in tumor-infiltrating leukocytes from colon cancer patients.
Cancer. 1989 Dec 1;64(11):2238-42. doi: 10.1002/1097-0142(19891201)64:11<2238::aid-cncr2820641109>3.0.co;2-p.
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