IDIOTYPIC NETWORK IN MELANOMA

黑色素瘤中的独特网络

基本信息

批准号：
3175941
负责人：
SOLDANO FERRONE
金额：
$ 22.46万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1983
资助国家：
美国
起止时间：
1983-12-01 至 1997-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3175941
关键词：
antigen antibody reaction antiidiotype antibody human tissue laboratory mouse laboratory rabbit laboratory rat melanoma molecular cloning monoclonal antibody neoplasm /cancer immunotherapy protein structure function tissue /cell culture tumor antigens

项目摘要

The long range goal of this proposal is to characterize the molecular and functional properties of monoclonal antibodies (MoAb) elicited by antiidiotypic MoAb which bear the internal image of human high molecular weight-melanoma associated antigen (HMW-MAA) and GD3 ganglioside. The latter two antigens are being used as targets for immunotherapy in patients with melanoma. The outlined studies will take advantage of a unique panel of antiidiotypic and antiantiidiotypic MoAb elicited during the previous grant period. We will analyze the genetic control of the humoral anti HMW- MAA immune response elicited y the antiidiotypic MoAb elicited with MoAb MK2-23 which bears the internal image of HMW-MAA. This information may suggest criteria to select patients who are likely to mount an anti HMW-MAA immune response following immunization with MoAb MK2-23. We will define the molecular basis of the specificity of antiantiidiotypic MoAb elicited with MoAb MK2-23 by correlating their antigen binding activity with the sequence of the variable regions of their heavy and light chains. Sequences may be identified which are potentially important for HMW-MAA binding activity of MoAb. We will humanize the mouse antiidiotypic MoAb MK2-23, which is being used as an immunogen in clinical trials, to overcome the problem of the formation of antimouse Ig antibodies. We will analyze the immunogenicity of humanized MoAb MK2-23, since this information will be useful to optimize the immunization schedule in patients with melanoma. We will characterize antiidiotypic MoAb elicited with the anti GD2 ganglioside MoAb MB3.6 and we will identify those which bear the internal image of CD3 ganglioside. We will correlate the sequences of the variable regions of the heavy and light chains of antiidiotypic MoAb with their immunogenic properties to define the structure-function relationship of these molecules. Lastly, we will determine the ability of antiidiotypic MoAb to modulate the immune lysis of melanoma cells mediated by anti GD3 ganglioside antibodies. the outlined studies will provide for the first time information about the structural and functional characteristics of the idiotype cascade in the HMW-MAA and in the GD3 ganglioside systems. Furthermore, the potential role of the idiotypic network in the effect of anti GD3 ganglioside immunity on the course of the disease will be characterized.

该提案的长期目标是表征分子和单克隆抗体 (MoAb) 的功能特性具有人类高分子内部图像的抗独特型单克隆抗体体重黑色素瘤相关抗原 (HMW-MAA) 和 GD3 神经节苷脂。这后两种抗原被用作患者免疫治疗的靶标患有黑色素瘤。概述的研究将利用一个独特的小组抗独特型和抗抗独特型MoAb在之前的过程中引发授予期。我们将分析体液抗HMW-的遗传控制 MAA 免疫反应由 MoAb 引发的抗独特型 MoAb 引发 MK2-23 带有 HMW-MAA 的内部图像。该信息可能建议选择可能进行抗 HMW-MAA 治疗的患者的标准 MoAb MK2-23 免疫后的免疫反应。我们将定义抗抗独特型 MoAb 特异性的分子基础通过将 MoAb MK2-23 的抗原结合活性与其重链和轻链可变区的序列。可以鉴定对 HMW-MAA 潜在重要的序列 MoAb 的结合活性。我们将小鼠抗独特型 MoAb 人源化 MK2-23，在临床试验中被用作免疫原，以克服抗小鼠 Ig 抗体形成的问题。我们将分析人源化 MoAb MK2-23 的免疫原性，因为该信息将对于优化黑色素瘤患者的免疫计划很有用。我们将表征用抗 GD2 神经节苷脂引发的抗独特型 MoAb MoAb MB3.6，我们将识别那些带有 CD3 内部图像的抗体神经节苷脂。我们将关联可变区的序列抗独特型 MoAb 的重链和轻链及其免疫原性属性来定义这些的结构-功能关系分子。最后，我们将确定抗独特型 MoAb 的能力调节抗 GD3 介导的黑色素瘤细胞的免疫裂解神经节苷脂抗体。概述的研究将提供第一个有关结构和功能特征的时间信息 HMW-MAA 和 GD3 神经节苷脂系统中的独特型级联。此外，独特型网络在影响中的潜在作用抗GD3神经节苷脂免疫对病程的影响会特点。