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神经氨酸酶与肿瘤免疫疗法

Neuraminidase and tumor immunotherapy.

作者信息

Sedlacek H H, Seiler F R, Schwick H G

出版信息

Klin Wochenschr. 1977 Mar 1;55(5):199-214. doi: 10.1007/BF01487712.

Abstract

Preliminary results of first clinical studies with the enzyme neuraminidase call attention to a new kind of cancer treatment. This promising approach to tumor immunotherapy was entered into the clinical phase as a consequence of successful experimental studies in tumor-bearing mice, rats and dogs. In this review, the presently known and essential results of experimental and clinical studies on tumor immunotherapy by means of neuraminidase are presented as well as some necessary and critical considerations in this context. Moreover, out of a broad variety of results of biochemical and biological in vitro studies, it was attempted to select the more essential knowledge which could contribute to a better understanding of the still rather unclear in vivo mode of action of the enzyme neuraminidase. In a first brief paragraph (1.0), the biochemically characteristic data of the enzyme neuraminidase is presented. In the second section (2.0), the basic knowledge about the effects of neuraminidase on cell behavior is rather amply contained. Here, on the one hand, the biophysical and biochemical alterations are mentioned, the so-called ""unmasking'' effects are reconsidered and, on the other hand, the effects on the immunologically responding cell are discussed. In a third section (3.0), the diverse findings from animal experiments using neuraminidase-treated tumor cells are confronted, whereby tumor transplantation experiments and tumor therapy experiments are dealt with separately. The last section (4.0) reports about the first clinical studies with neuraminidase-treated autologous as well as homologous tumor cells, which partly brought about rather surprising and astonishing success. On the basis of recent findings by the study group of the authors, the more prior and sometimes discrepant results of various groups are critically considered. The problems of alteration of antigenicity and of other properties of cells through splitting off membrane-bound neuraminic acid, the facts of adjuvanticity of neuraminidase itself, the relation of successful therapy to dose dependency as well as the relation of undesirable methods for tumor mass reduction to the immunological responsiveness of the tumor bearer were especially looked into.

摘要

对神经氨酸酶进行的首批临床研究的初步结果引起了人们对一种新型癌症治疗方法的关注。由于在荷瘤小鼠、大鼠和犬身上进行的实验研究取得成功,这种颇具前景的肿瘤免疫治疗方法进入了临床阶段。在这篇综述中,介绍了目前已知的关于通过神经氨酸酶进行肿瘤免疫治疗的实验和临床研究的重要结果,以及在此背景下一些必要且关键的思考。此外,从大量生化和生物学体外研究结果中,试图挑选出更重要的知识,这些知识有助于更好地理解神经氨酸酶在体内仍相当不清楚的作用方式。在第一段简要内容(1.0)中,介绍了神经氨酸酶的生化特征数据。在第二部分(2.0)中,相当充分地包含了关于神经氨酸酶对细胞行为影响的基础知识。一方面,提到了生物物理和生化改变,重新审视了所谓的“去掩蔽”效应,另一方面,讨论了对免疫反应细胞的影响。在第三部分(3.0)中,对比了使用经神经氨酸酶处理的肿瘤细胞进行动物实验的各种发现,其中肿瘤移植实验和肿瘤治疗实验分别进行了探讨。最后一部分(4.0)报告了对经神经氨酸酶处理的自体及同源肿瘤细胞进行的首批临床研究,这些研究部分取得了相当令人惊讶和意想不到的成功。基于作者研究小组的最新发现,批判性地考虑了各个小组先前的、有时存在差异的结果。特别研究了通过去除膜结合神经氨酸改变细胞抗原性和其他特性的问题、神经氨酸酶本身的佐剂作用事实、成功治疗与剂量依赖性的关系以及肿瘤块减少的不良方法与肿瘤携带者免疫反应性的关系。

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