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抗卵巢癌相关抗原单克隆抗体的临床应用

Clinical applications of monoclonal antibodies against ovarian cancer-associated antigens.

作者信息

Kenemans P, Yedema C A, Hilgers J H, Massuger L F, Verheijen R H, Thomas C M, Poels L G

机构信息

Department of Obstetrics and Gynaecology, Free University, Amsterdam, The Netherlands.

出版信息

Eur J Obstet Gynecol Reprod Biol. 1988 Nov;29(3):207-18. doi: 10.1016/s0028-2243(88)80025-x.

Abstract

Monoclonal antibodies (McAbs), reactive with tumour-associated antigens (TAAs) present on tumour cells, appear to offer new possibilities in the diagnosis and treatment of cancer (Table I). In addition to these prospects for clinical application, monoclonal antibodies also serve as useful instruments in basic cancer research. The hybridoma technology initiated by Köhler and Milstein in 1975, underwent a very rapid development and has now shown its potential in the field of oncology. This technique made it possible to produce very large quantities of homogeneous antibodies of a stable quality. These McAbs often recognize only one antigenic determinant, or epitope, of cell surface and other molecules. This high specificity is essential for in vivo applications, especially in therapeutic immunotargeting. A central question is whether the antibodies can reach and identify those antigens on ovarian tumour cells that are not shared with normal tissues. Various antibodies have been described in the field of gynaecological oncology, which are assumed to be capable of recognizing such ovarian tumour-related antigens. These McAbs, single or in combination, are capable of showing, unambiguously, the presence of various tumour-associated antigens on ovarian carcinoma cells either in tissue or, when antigen shedding occurs, in blood. However, these McAbs may also react with tumour-associated antigens present on endometrial, cervical, colorectal, breast or other carcinoma cells. The original immunogens used to generate these McAbs differ as to their origin: ovarian cancer cells, breast cancer cells, human milk-fat preparations, trophoblastic cells, endometrial cancer cells have been used as well as osteogenic sarcoma cells, epidermoid carcinoma cells and small-cell lung cancer, colorectal, pancreatic and laryngeal carcinoma cells. The histological distribution patterns of the antigens recognized by these McAbs vary widely: cross-reactions with normal tissue and with carcinomas different from those used as immunogen are frequently seen.

摘要

与肿瘤细胞上存在的肿瘤相关抗原(TAA)发生反应的单克隆抗体(McAb),似乎为癌症的诊断和治疗提供了新的可能性(表I)。除了这些临床应用前景外,单克隆抗体在基础癌症研究中也是有用的工具。1975年由科勒和米尔斯坦开创的杂交瘤技术发展非常迅速,现已在肿瘤学领域展现出其潜力。这项技术使得能够大量生产质量稳定的同质抗体。这些单克隆抗体通常只识别细胞表面和其他分子的一个抗原决定簇或表位。这种高特异性对于体内应用至关重要,尤其是在治疗性免疫靶向方面。一个核心问题是这些抗体能否到达并识别卵巢肿瘤细胞上那些正常组织所没有的抗原。妇科肿瘤学领域已经描述了各种抗体,据推测它们能够识别此类卵巢肿瘤相关抗原。这些单克隆抗体单独或联合使用,能够明确显示卵巢癌细胞上各种肿瘤相关抗原的存在,无论是在组织中,还是在发生抗原脱落时在血液中。然而,这些单克隆抗体也可能与子宫内膜、宫颈、结肠、乳腺或其他癌细胞上存在的肿瘤相关抗原发生反应。用于产生这些单克隆抗体的原始免疫原在来源上各不相同:卵巢癌细胞、乳腺癌细胞、人乳脂肪制剂、滋养层细胞、子宫内膜癌细胞以及骨肉瘤细胞、表皮样癌细胞和小细胞肺癌、结肠、胰腺和喉癌细胞都曾被使用。这些单克隆抗体所识别抗原的组织学分布模式差异很大:经常可见与正常组织以及与用作免疫原的癌不同的癌发生交叉反应。

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