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用小鼠单克隆抗体腹腔内治疗的卵巢癌患者中抗肿瘤抗原和自身抗原的抗独特型抗体的产生

Development of anti-idiotypic antibodies against tumour antigens and autoantigens in ovarian cancer patients treated intraperitoneally with mouse monoclonal antibodies.

作者信息

Courtenay-Luck N S, Epenetos A A, Sivolapenko G B, Larche M, Barkans J R, Ritter M A

机构信息

Department of Clinical Oncology, Royal Postgraduate Medical School, Hammersmith Hospital, London.

出版信息

Lancet. 1988 Oct 15;2(8616):894-7. doi: 10.1016/s0140-6736(88)92482-8.

Abstract

Repeated intraperitoneal administration of therapeutic amounts of radiolabelled (iodine-131) murine monoclonal antibodies leads to the development of an immune response in the recipient, part of which is directed against the variable region (idiotype) of the administered antibody (anti-Id1 response). Human immunoglobulin purified from these patients inhibits binding of the original murine monoclonal antibody to its target tumour antigen and therefore represents an "internal image" of the tumour antigen. Furthermore, this study recorded the development of human antibodies that themselves bind to the tumour antigen, with a specificity identical or similar to that of the injected monoclonal antibody. These human antitumour antibodies are probably generated by way of the idiotypic network and confirm the existence of the idiotypic network. Accompanying this antitumour response the transient development of autoantibodies that react with connective tissue components of liver, kidney, spleen, and diaphragm was also observed.

摘要

多次腹腔注射治疗剂量的放射性标记(碘-131)鼠单克隆抗体可导致受体产生免疫反应,其中部分免疫反应针对所注射抗体的可变区(独特型)(抗独特型1反应)。从这些患者体内纯化的人免疫球蛋白可抑制原始鼠单克隆抗体与其靶肿瘤抗原的结合,因此代表了肿瘤抗原的“内影像”。此外,该研究记录了人抗体自身与肿瘤抗原结合的情况,其特异性与注射的单克隆抗体相同或相似。这些人抗肿瘤抗体可能是通过独特型网络产生的,证实了独特型网络的存在。伴随着这种抗肿瘤反应,还观察到了与肝、肾、脾和膈肌结缔组织成分发生反应的自身抗体的短暂产生。

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