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Biochemical and Immunological Characterization of Tumors by Immunoscintigraphy

通过免疫闪烁扫描法对肿瘤进行生化和免疫学表征

基本信息

批准号：
63570496
负责人：
NAKAMURA Kayoko
金额：
$ 1.34万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

项目摘要

Immunoscintigraphy has been exclusively studied, since many monoclonal antibodies associated with tumors have been developed. Many factors are involved in the accumulation of antibody into the tumors; Especially characteristics of tumors, such as their vascularity, the antigen level, sites to produce antigens, and presence of necrosis, affect the localization of injected antibody. In other words, biodistributions of injected antibodies reflect the variabilities and specificities of tumors. Standing at this point, we have intended to clarify biochemical and immunological properties of tumor through immunoscintigraphies of several kinds of tumors. We also reviewed radioimmunodetection: its problems and future. In these reviews, we have pointed out factors which influenced the localization of antibodies into tumors. Two factors have been picked up here. One is the effect of circulating an tigen and the other is that of antigen expression. Using tumor models which consisted of the human he … More patocellular carcinoma, NuE and PLC cell lines producing AFP xenografted in nude mice, and I-125-labeled monoclonal antibody 19FI2 raised against AFP, following results were obtained.(1) Endogeneous circulating antigen retained the antibody in the whole body for a longer period. The ability of monoclonal antibodies to target tumors was influenced not only by how much antigen was present but also how rapid antigen was cleared in the blood. (2) Treatment of NuE with interferon (IFN) alphaA increased the surface expression of AFP in an IFN-alphaA dose dependent manner. The IFN-alphaA treatment substantially increased the localization of labeled 19FI2 to the NuE grown in athmic mice.It could be said that adequate tumors and monoclonal antibodies for immunoscintigraphy were tumors which excreate few antigen endogeneously, and antibodies that recognize antigen present in the surface of tumor cells. Co- administration of biological response modifiers, such as interferon, together with antibody is very promising not only since they would change the biodistribution but also since they might reduce the side effects caused by the injection of antibody. Less

由于许多与肿瘤相关的单克隆抗体已经被开发出来，免疫扫描已经被专门研究。抗体在肿瘤中的积累涉及多种因素；特别是肿瘤的特征，如它们的血管性、抗原水平、产生抗原的部位和坏死的存在，都会影响注射抗体的定位。换句话说，注射抗体的生物分布反映了肿瘤的可变性和特异性。站在这一点上，我们打算通过几种肿瘤的免疫成像来阐明肿瘤的生化和免疫学特性。并对放射免疫检测存在的问题和前景进行了综述。在这些综述中，我们指出了影响抗体在肿瘤中定位的因素。这里提到了两个因素。一个是循环抗原的作用，另一个是抗原表达的作用。以人肝癌为肿瘤模型，将产生AFP的NuE和PLC细胞系移植到裸鼠体内，培养i -125标记的抗AFP单克隆抗体19FI2，得到以下结果：(1)内源性循环抗原将抗体在全身保留较长时间。单克隆抗体靶向肿瘤的能力不仅受存在多少抗原的影响，还受血液中抗原被清除的速度的影响。(2)干扰素(IFN) α a治疗NuE可增加AFP的表面表达，并呈剂量依赖性。ifn - α处理显著增加了在哮喘小鼠中生长的NuE中标记19FI2的定位。可以说，适合于免疫显像的肿瘤和单克隆抗体是内源性产生少量抗原的肿瘤和识别存在于肿瘤细胞表面抗原的抗体。生物反应调节剂（如干扰素）与抗体联合使用，不仅可以改变生物分布，而且可以减少注射抗体引起的副作用，因此具有广阔的应用前景。少