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[抗独特型单克隆抗体治疗晚期黑色素瘤的临床试验]

[Clinical trial of anti-idiotypic monoclonal antibodies in advanced melanoma].

作者信息

Kageshita T, Hirai S, Ono T

机构信息

Dept. of Dermatology, Kumamoto University School of Medicine.

出版信息

Gan To Kagaku Ryoho. 1994 Feb;21(2):163-9.

PMID:8311486
Abstract

In this study, first the background of idiotype network and characterization of high molecular weight-melanoma associated antigen (HMW-MAA) was reviewed. Second, the development and characterization of syngeneic anti-idiotypic monoclonal antibodies (anti-Id mAb) against anti-HMW-MAA mAb was described. Among them, anti-Id mAb MK2-23 and TK7-371 were shown to have the internal image of HMW-MAA, since they induced anti-anti Id antibody that reacts with HMW-MAA and also delayed type hypersensitivity to melanoma cells. Third, the results of clinical trial with anti-Id mAb in patients with advanced melanoma was described. Among 60 patients, 7 showed clinical response (CR 1, PR 3, MR 3). The survival of patients who developed anti-HMW-MAA Ab was significantly longer than in patients without detectable anti-HMW-MAA Ab. Moreover, anti-Id mAb immunized the patients after removal of metastatic lesions. The disease-free interval of patients who developed high titer of anti-anti Id Ab was significantly longer than that of those with low titer of the Ab. These results suggest that the anti-Id mAb may be a useful reagent for active specific immunotherapy of melanoma.

摘要

在本研究中,首先回顾了独特型网络的背景以及高分子量黑色素瘤相关抗原(HMW-MAA)的特征。其次,描述了针对抗HMW-MAA单克隆抗体的同基因抗独特型单克隆抗体(抗Id mAb)的研发及特性。其中,抗Id mAb MK2-23和TK7-371显示具有HMW-MAA的内影像,因为它们诱导出与HMW-MAA反应的抗抗Id抗体,并且还引发对黑色素瘤细胞的迟发型超敏反应。第三,描述了抗Id mAb在晚期黑色素瘤患者中的临床试验结果。在60例患者中,7例出现临床反应(完全缓解1例,部分缓解3例,疾病稳定3例)。产生抗HMW-MAA抗体的患者的生存期明显长于未检测到抗HMW-MAA抗体的患者。此外,抗Id mAb在清除转移病灶后对患者进行免疫。产生高滴度抗抗Id抗体的患者的无病生存期明显长于产生低滴度该抗体的患者。这些结果表明,抗Id mAb可能是黑色素瘤主动特异性免疫治疗的一种有用试剂。

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