RESEARCH FOR CLINICAL APPLICATION OF ANTI-IDIOTYPIC MONOCLONAL ANTIBODIES.

抗独特型单克隆抗体的临床应用研究。

基本信息

批准号：
02670483
负责人：
KAGESHITA Toshiro
金额：
$ 1.6万
依托单位：
KUMAMOTO UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

1) Detection of anti-melanoma antibodies in serum of melanoma patients. High molecular weight-melanoma associated antigen (HMW-MAA) is one of human melanoma associated antigen and is thought to be poorly immunogenic. In this study we have developed new system to detect for the anti-HMW-MAA antibodies in serum of melanoma patients using anti-idiotypic monoclonal antibodies (anti-Id mAb) to anti-HMW-MAA mAb. In this new system, anti-HMW-MAA antibodies were found in 20% and 40% of serum of melanoma patients with stage 1 and 4 respectively and was not found in healthy normal control. These results suggest that HMW-MAA could elicit the immune response in some melanoma patients.2) Immunogenicity of anti-Id mAb. The anti-Id mAb, which bears the internal image of HMW-MAA, was injected into BALB/C mouse three times and serological and immunochemical analysis was done using mouse serum. The serum reacted only cultured melanoma cell. Furthermore, serum immunoprepicitate the same band from radiolabeled melanoma cells with anti-HMW-MAA mAb on SDS-PAGE.Cultured melanoma cells were injected into the right foot pad which mouse already immunized with anti-Id mAb and culture lymphoid cells were injected into the left side as control. Swelling of foot pad were measured and anti-Id mAb can induce the delayed type hypersensitivity.These results suggest that anti-Id mAb can induce both humoral and cellular immune response against the HMW-MAA.3) Immunohistochemistry for anti-anti-Id mAb. Anti-anti-Id mAb were developed from the mouse immunized anti-Id mAb which bears the internal image of HMW-MAA. The anti-anti-Id mAb display similar reactivity patterns with surgically removed melanoma lesions.

1）在黑色素瘤患者血清中检测抗黑色素瘤抗体。高分子量黑色素瘤相关抗原（HMW-MAA）是人黑色素瘤相关的抗原之一，被认为是免疫原性的。在这项研究中，我们开发了使用抗IDiotypic的单克隆抗体（抗ID MAB）对抗HMW-MAA MAB的抗HMW患者血清患者血清中抗HMW-MAA抗体的新系统。在这个新系统中，分别在20％和40％的患有1和4期的黑色素瘤患者血清中发现了抗HMW-MAA抗体，在健康的正常对照中未发现。这些结果表明，HMW-MAA可以引起一些黑色素瘤患者的免疫反应。2）抗ID MAB的免疫原性。带有HMW-MAA内部图像的抗ID MAB被注入BALB/C小鼠3次，并使用小鼠血清进行血清学和免疫化学分析。血清仅反应培养的黑色素瘤细胞。此外，在SDS-PAGE上用抗HMW-MAA MAB从放射性标记的黑色素瘤细胞中从放射性标记的黑色素瘤细胞中获得同一带的血清免疫反应。培养的黑色素瘤细胞被注入右脚垫中，该细胞已注入了已经用抗ID MAB和抗培养的MAB和培养的淋巴样细胞免疫的小鼠。左侧作为控制。测量脚垫的肿胀并抗ID mAb可以诱导延迟的型高敏性。这些结果表明，抗ID MAB可以针对HMW-MAA诱导体液和细胞免疫反应。。抗Anti-ID mAb是由带有HMW-MAA内部图像的小鼠免疫抗ID MAB开发的。抗Anti-ID MAB显示出类似的反应性模式，并通过手术去除黑色素瘤病变。