Reactivation of human cells for novel fully human Ab platform

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年全球增长率为37%。自1975年被发现以来，单克隆抗体被描述为“神奇的子弹”，具有寻找和靶向特定分子并以高亲和力结合它们的潜力。使用啮齿动物系统开发用于人类的mAb的早期治疗工作被证明是无效的，因为它们在人类中引起强烈的免疫应答，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源性mAb的人源化和完全hu-mAb的开发。市场上有24种mAb治疗药物，mAb占FDA管道中现有药物的25%以上，占所有新药上市的约50%。目前用于hu-mAb开发的技术是次优的，因为源自这些方法的治疗剂是1）不完全人的，导致毒性增加，或2）由于实现高亲和力而需要几轮成熟，导致更长时间、更昂贵的开发。 该I期提案的目标是使我们的专利鼠再活化平台适应在SCID-huPBL小鼠背景下免疫的人B细胞，最终导致开发全人mAb的新方法（人再活化）。再活化技术是一种优先选择、富集和扩增人源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mAb的快速，高效和成本效益的开发，增加这些试剂对研究癌症和其他致命疾病的药物发现研究人员的可及性。 公共卫生相关性：治疗性单克隆抗体正在成为疾病治疗中最有效的靶向药物方法之一。NeoClone正在计划调整其成功的单克隆抗体再活化技术，以开发全人治疗性单克隆抗体。该资助的成功完成将证明以低成本开发高亲和力全人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的各种疾病。这种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提供巨大的经济效益，并最终降低医疗保健成本，同时改善患者的预后。

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.