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The analysis of immune response and cytotoxic mechanism with use of anti-ICAM-1 monoclonal antibodies

使用抗ICAM-1单克隆抗体分析免疫反应和细胞毒机制

基本信息

批准号：
03670330
负责人：
TSUJISAKI Masayuki
金额：
$ 1.34万
依托单位：
Sapporo Medical College
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670330/
关键词：
adhesion modecule ICAM-1 circulating antigen cytotoxic mechanism metastasis and invasion of cancer cells ICAMー1 モノクロ-ナル抗体

项目摘要

A new monoclonal antibody (MoAb) HA58 (IgGl) was prepared, which recognizes the binding site on the intercellular adhesion molecule-1 (ICAM-1) antigen to the lymphocyte function-associated antigen-1 (LFA-1). The double-determinant immunoassay (DDIA) was established with use of MoAb HA58 and another anti-ICAM-1, MoAb CL207, to detect the soluble, shedding ICAM-1 antigen. The incidence of positivity for ICAM-1 antigen in malignant diseases was higher than that in benign diseases or in healthy controls. Immunostaining of cancerous tissue with MoAb HA58 showed that the ICAM-1 antigen was expressed not only on malignant cells but also on stromal cells (mainly fibroblasts) near cancer nests, and the stromal cells immediately adjacent to cancer nests, in comparison to those cells farther away from the nests, have a higher ICAM-1 expression. We speculate that tumor cells activate T cells to produce cytokines (e.g.IFN-gamma), resulting in strong expression of the ICAM-1 on surrounding fibroblasts, as well as on tumor cells. Shedding ICAM-1 antigen may also block the attachment of cytotoxic T cells and/or NK cells to cancer cells, since LFA-1 could be blocked with soluble ICAM-1. This could be one of the escape mechanisms of cancer cells from the immunosurveillance system of the host.

制备了一种识别细胞间黏附分子-1(ICAM-1)抗原与淋巴细胞功能相关抗原-1(LFA-1)结合部位的单抗(Moab)HA58(IgG1)。用单抗HA58和另一抗ICAM-1的单抗CL207建立了双决定簇免疫分析(DDIA)来检测可溶性、脱落的ICAM-1抗原。恶性疾病组ICAM-1抗原阳性率明显高于良性疾病组和健康对照组。Moab HA58免疫组织化学染色显示，ICAM-1抗原不仅在癌巢附近的癌细胞上表达，而且在癌巢附近的间质细胞(主要是成纤维细胞)上也有表达，与远离癌巢的间质细胞相比，紧邻癌巢的间质细胞有更高的ICAM-1表达。我们推测，肿瘤细胞激活T细胞产生细胞因子(如干扰素-γ)，导致周围成纤维细胞和肿瘤细胞上ICAM-1的强烈表达。去除ICAM-1抗原也可能阻止细胞毒性T细胞和/或NK细胞与癌细胞的附着，因为LFA-1可以被可溶性ICAM-1阻断。这可能是癌细胞逃避宿主免疫监视系统的机制之一。