Reactivation of human cells for novel fully human Ab platform

描述（由申请人提供）：单克隆抗体（mab）已发展成为一类非常有效的治疗分子，在2001年至2002年期间全球增长了37%。自1975年发现单克隆抗体以来，单克隆抗体被称为“魔弹”，具有寻找和靶向特定分子并以高亲和力结合它们的潜力。利用啮齿动物系统开发用于人类的单克隆抗体的早期治疗工作被证明是无效的，因为它们在人体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鼠源单抗的人源化和全人单抗的开发。目前市场上有24种单克隆抗体治疗药物，单克隆抗体占目前FDA审批药物的25%以上，占所有新上市药物的50%左右。目前开发hu- mAb的技术不是最优的，因为从这些方法衍生的治疗方法要么1)不完全适合人类，导致毒性增加，要么2)由于达到高亲和力，需要几轮成熟，导致开发时间更长，成本更高。

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.