DEVELOPMENT OF ANTICO RECEPTOR MABS FOR HIV THERAPY

用于 HIV 治疗的 Antico 受体 MABS 的开发

• 批准号: 2793411
• 负责人: PAUL J MADDON
• 金额: $ 52.06万
• 依托单位: PROGENICS PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-08-14 至 2002-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2793411
• 关键词: Macaca; antiAIDS agent; chemokine; cytokine receptors; drug design /synthesis /production; immunological substance; monoclonal antibody; receptor expression

DESCRIPTION: (Adapted from P.I.'s abstract). A major goal of HIV research is the development of new antiviral agents that target distinct stages of the viral replicative cycle. Recently, fusion of HIV-1 with host cell membranes has been shown to require certain human "co-receptor" molecules that belong to the chemokine receptor family of seven transmembrane-spanning (7-TM), G protein-coupled receptors. These molecules provide excellent targets for the majority of currently licensed pharmaceuticals. The overall goal of this project is to determine whether anti-co-receptor monoclonal antibodies (mAbs), used alone or in combination with other antiviral agents, can effectively inhibit HIV-1 replication in vitro and protect against infection in vivo using the best systems available. In the Phase I project, mAbs to the CCR5 co-receptor were generated that potently inhibit HIV-1 entry without affecting normal CCR5 activity. In the Phase II project, HIV-1 inhibitor mAbs will be generated to additional chemokine receptor molecules known to support the entry of a wide range of viral isolates. The mAbs will be extensively evaluated for biologic properties and their breadth, potency and mechanism of antiviral activity. The potential for HIV-1 to develop resistance by altering its patterns of co-receptor usage will be explored in an extensive series of in vitro studies. Specific combinations of anti-co-receptor mAbs and other antiviral agents will be examined for possible synergistic activity in preventing HIV-1 infection and the development of drug resistant mutants. MAbs and combinations that provide the most broad, potent, and sustained inhibition of HIV-1 in vitro will evaluated in vivo in the hu-PBL-SCID and SHIV-macaque models of HIV-1 infection. Here specific regimens will be tested for the ability to protect animals against infection by viruses derived from diverse HIV-1 isolates. If successful, this project would guide our selection of mAbs to be humanized and advanced into clinical development as novel agents for the treatment and prophylaxis of HIV-1 infection. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE

描述：(改编自P.I.的抽象)。艾滋病研究的一个主要目标是