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使用针对T细胞抗原受体Vβ链的单克隆抗体进行体内T细胞肿瘤治疗。

In vivo T cell tumor therapy with monoclonal antibody directed to the V beta chain of T cell antigen receptor.

作者信息

Kanagawa O

机构信息

Lilly Research Laboratory, La Jolla, California 92037.

出版信息

J Exp Med. 1989 Nov 1;170(5):1513-9. doi: 10.1084/jem.170.5.1513.

Abstract

To test whether antibodies directed to TCR affect T cell tumor growth in vivo, mice were inoculated intravenously with C6VL tumor cells expressing V beta 6 TCR and then treated intraperitoneally with mAb specific for V beta 6 TCR. Administration of anti-V beta 6 antibody prolonged survival of mice bearing V beta 6-expressing tumor cells and it led to the induction of host immunity to the tumor cells in surviving animals. This treatment eliminated not only tumor cells bearing V beta 6 TCR but also normal host T cells expressing V beta 6 T cells receptors. However, the lack of V beta 6-expressing T cells in such treated mice did not result in generalized immune disfunction. These data demonstrate the utility of anti-TCR V segment antibody in the treatment of T cell tumors. Most importantly, since the number of V genes for the T cell antigen receptor is limited, both in man and in mouse, it should be possible to establish a panel of mAbs directed to each V gene product and use such antibodies in the treatment of T cell neoplasms.

摘要

为了检测针对TCR的抗体是否会影响体内T细胞肿瘤的生长,给小鼠静脉注射表达Vβ6 TCR的C6VL肿瘤细胞,然后腹腔注射针对Vβ6 TCR的单克隆抗体。给予抗Vβ6抗体可延长携带表达Vβ6肿瘤细胞的小鼠的生存期,并导致存活动物对肿瘤细胞产生宿主免疫。这种治疗不仅消除了携带Vβ6 TCR的肿瘤细胞,还消除了表达Vβ6 T细胞受体的正常宿主T细胞。然而,经这种处理的小鼠中缺乏表达Vβ6的T细胞并未导致全身性免疫功能障碍。这些数据证明了抗TCR V区抗体在治疗T细胞肿瘤中的效用。最重要的是,由于人及小鼠中T细胞抗原受体的V基因数量有限,应该有可能建立一组针对每种V基因产物的单克隆抗体,并将此类抗体用于治疗T细胞肿瘤。

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