Reactivation of human cells for novel fully human Ab platform

新型全人抗体平台重新激活人体细胞

基本信息

批准号：
8319829
负责人：
Rachel Hannah Kravitz
金额：
$ 28.64万
依托单位：
NEOCLONE BIOTECHNOLOGY INTERNATIONAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-01 至 2014-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8319829
关键词：
Accounting Address Affinity Allergic Reaction Anaphylaxis Antibodies Antibody Affinity Antibody-Producing Cells Antigen Targeting Antigens Autoimmune Process B-Lymphocytes Binding Biological Assay Biotechnology Cells Clinical Communicable Diseases Custom Development Disease Drug Delivery Systems Early treatment Economics Eligibility Determination Engraftment Evaluation Goals Government Grant Growth Half-Life Harvest Health Care Costs Human Immune response Immunization Immunoglobulin Class Switching Immunoglobulins In Vitro Interferometry International Legal patent Lymphocyte Magic Malignant Neoplasms Marketing Measurable Metabolic Clearance Rate Methods Modeling Monoclonal Antibodies Mus Outcome Patients Persons Pharmaceutical Preparations Phase Positioning Attribute Process Productivity Protocols documentation Reagent Relative (related person)Research Research Personnel Rodent S100A9 gene Screening procedure Spleen Splenocyte Staging System Technology Testing Therapeutic Therapeutic Agents Therapeutic Monoclonal Antibodies TimeLine Toxic effect Wages cost cytokine drug development drug discovery human monoclonal antibodies improved innovation innovative technologies meetings novel novel therapeutics success therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Monoclonal antibodies (mAbs) have been developed into a highly effective class of therapeutic molecules, with global growth of 37% between 2001 and 2002. Since their discovery in 1975, mAbs have been described as "magic bullets" with the potential to seek out and target specific molecules and bind them with high affinity. Early treatment efforts using rodent systems to develop mAbs for use in humans proved ineffective due to the strong immune responses they elicit in humans, limiting their half life in the body and potentially causing anaphylaxis. Strategies to overcome this obstacle have included humanization of rodent-derived mAbs and development of fully hu-mAbs. There are 24 mAb therapeutics on the market, and mAbs account for more than 25% of the current drugs in the FDA pipeline and ~50% of all new drug launches. Current technologies for hu- mAb development are sub-optimal in that the therapeutics derived from these approaches are either 1) not fully human resulting in increased toxicity, or 2) require several rounds of maturation due to achieve high affinity resulting in longer, more costly development. The goal of this Phase I proposal is to adapt our patented murine reactivation platform to human B cells immunized in the context of the SCID-huPBL mouse, ultimately leading to a new method (human reactivation) for the development of fully-human mAbs. Reactivation is the technology for selecting, enriching, and amplifying human high affinity antibody producing cells preferentially. Successful completion of this proposal will result in the rapid, efficient, and cos effective development of fully-human high affinitity mAbs, increasing the accessibility of these reagents to drug discovery researchers investigating cancer and other deadly diseases. PUBLIC HEALTH RELEVANCE: Therapeutic monoclonal antibodies are emerging as one of the most effective targeted drug approaches for disease treatment. NeoClone is proposing to adapt its successful monoclonal antibody reactivation technology to enable development of fully-human therapeutic monoclonal antibodies. Successful completion of this grant will demonstrate the feasibility of developing high affinity fully-human therapeutic monoclonal antibodies at low cost, that can be broadly used to treat a variety of diseases, ranging from cancer to infectious disease. The availability of such a powerful therapeutic development platform will provide immense economic benefit by reducing costs associated with drug development, and ultimately lowering healthcare costs while improving the patients' outcome.

描述（由申请人提供）：单克隆抗体 (mAb) 已发展成为一类高效的治疗分子，2001 年至 2002 年间全球增长了 37%。自 1975 年发现以来，mAb 被描述为“神奇子弹”具有寻找和靶向特定分子并以高亲和力结合它们的潜力。早期使用啮齿动物系统开发用于人类的单克隆抗体的治疗努力被证明是无效的，因为它们在人类中引起强烈的免疫反应，限制了它们在体内的半衰期并可能引起过敏反应。克服这一障碍的策略包括啮齿动物来源的单克隆抗体的人源化和全人单克隆抗体的开发。市场上有 24 种 mAb 疗法，mAb 占 FDA 现有药物的 25% 以上，占所有新药上市的约 50%。目前的 hu-mAb 开发技术并不是最理想的，因为这些方法衍生的治疗方法要么是 1) 不完全是人源的，导致毒性增加，要么 2) 由于实现高亲和力而需要几轮成熟，导致时间更长、成本更高发展。这一第一阶段提案的目标是使我们的专利小鼠再激活平台适应在 SCID-huPBL 小鼠中免疫的人类 B 细胞，最终形成一种用于开发全人单克隆抗体的新方法（人类再激活）。再激活是优先选择、富集和扩增人类高亲和力抗体产生细胞的技术。该提案的成功完成将导致全人类高亲和力单克隆抗体的快速、高效和经济有效的开发，从而增加研究癌症和其他致命疾病的药物发现研究人员对这些试剂的可及性。公共卫生相关性：治疗性单克隆抗体正在成为疾病治疗最有效的靶向药物方法之一。 NeoClone 提议采用其成功的单克隆抗体再激活技术来开发全人治疗性单克隆抗体。这笔资金的成功完成将证明以低成本开发高亲和力全人源治疗性单克隆抗体的可行性，该抗体可广泛用于治疗从癌症到传染病等多种疾病。如此强大的治疗开发平台的可用性将通过降低与药物开发相关的成本来提供巨大的经济效益，并最终降低医疗成本，同时改善患者的治疗结果。