CLONING HUMAN ANTI-GP120 B CELLS FOR AIDS THERAPY

克隆人类抗 GP120 B 细胞用于艾滋病治疗

• 批准号: 3489496
• 负责人: HEINZ KOHLER
• 金额: $ 5万
• 依托单位: IDEC PHARMACEUTICALS CORPORATION
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3489496
• 关键词: AIDS therapy; B lymphocyte; CD4 molecule; HIV envelope protein gp120; HIV infections; T lymphocyte; antiAIDS agent; antiantibody; antibody formation; binding proteins; clone cells; diagnosis design /evaluation; epitope mapping; molecular cloning; monoclonal antibody; neutralizing antibody; tissue /cell culture

DESCRIPTION: (Adapted from the applicant's abstract) HIV infection is characterized by a long asymptomatic state during which the immune state of the infected individual is not clinically impaired. During this time, neutralizing antibodies may play an important role in controlling virus replication and thereby maintaining the disease-free state. The major neutralizing epitope of HIV is the highly variable V3 loop region of gpl20 while a weaker set of epitopes is in the conserved CD4-related region. For passive immunotherapy in AIDS, group-specific neutralizing antibodies are preferred. The aim of this project is to develop human group-specific neutralizing antibodies against a conserved CD4-related epitope. B cells obtained from the peripheral blood of HIV+ individuals will be enriched using anti-idiotypic antibodies previously shown to select for group-specific neutralizing antibodies. B cells from individuals with high titers of group-specific/Id+ antibodies will be clonally expanded using anti-CD3 activated T cells, a highly efficient B cell cloning system. B cell colonies producing antibodies of the appropriate specificity will be transformed using EBV to establish short-term clones which will be further evaluated. Immunoglobulin genes from B cells found to produce group-specific neutralizing antibodies will be cloned and expressed to produced antibody for clinical evaluation to be initiated during Phase II studies.

描述：（改编自申请人摘要）HIV感染是 其特征在于长时间的无症状状态，在此期间， 受感染的个体在临床上没有受损。 在这段时间内， 中和抗体可能在控制病毒方面起重要作用 复制，从而保持无病状态。 主要 HIV的中和表位是gp 120的高度可变的V3环区 而一组较弱的表位位于保守的CD 4相关区域。 为 被动免疫疗法在艾滋病，群体特异性中和抗体， preferred. 该项目的目的是开发人类群体特异性 针对保守的CD 4相关表位的中和抗体。 B细胞 将从HIV+个体的外周血中获得的 使用先前显示的抗独特型抗体选择 群体特异性中和抗体。 来自高血压患者的B细胞 将使用克隆扩增组特异性/Id+抗体的滴度 抗CD 3活化的T细胞，一种高效的B细胞克隆系统。 B 产生适当特异性抗体的细胞集落将被 使用EBV转化以建立短期克隆， 评估。 发现来自B细胞的免疫球蛋白基因产生 将克隆和表达组特异性中和抗体， 在第II阶段启动临床评价的抗体生产 问题研究