NOVEL BISPECIFIC ANTIBODIES FOR FACILITATING SITE SPECIFIC TISSUE REPAIR

促进位点特异性组织修复的新型双特异性抗体

基本信息

批准号：
7725256
负责人：
Leslie P Cousens
金额：
$ 5.29万
依托单位：
ROGER WILLIAMS HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-06-05 至 2009-04-30
项目状态：
已结题

项目摘要

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Bispecific antibody technology has the potential to combine effector cells that may modulate the rate of wound healing with a specific injury-targeting antibody to create a biologic "drug" for the purpose of enhancing wound repair. We will combine (chemically heteroconjugate) one mAb specific for macrophages with a second mAb directed at fibrinopeptide, which is an injury-specific antigen released at the site of a wound within minutes of injury. The resulting bispecific antibody (BiAb) with the ability to simultaneously bind to both macrophages and fibrinopeptide, "MFibBi", will be used to "arm" macrophage populations ex vivo for administration in the mouse tail-injury model. Hypothesis: Targeting of macrophages to a wound with bispecific antibodies will accelerate wound healing. Specific Aims: 1) To produce and validate MFiBi. 2) To characterize cytokine-matured macrophage populations. 3) To target macrophages to experimentally induced wounds using MFiBi.

该子项目是利用该技术的众多研究子项目之一资源由 NIH/NCRR 资助的中心拨款提供。子项目及研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金，因此可以在其他 CRISP 条目中表示。列出的机构是对于中心来说，它不一定是研究者的机构。双特异性抗体技术有可能将调节伤口愈合速度的效应细胞与特定的损伤靶向抗体结合起来，创造出一种生物“药物”，以增强伤口修复。我们将一种针对巨噬细胞的 mAb 与另一种针对纤维蛋白肽的 mAb 结合（化学杂合物），纤维蛋白肽是一种损伤特异性抗原，在受伤后几分钟内在伤口部位释放。由此产生的双特异性抗体（BiAb）能够同时结合巨噬细胞和纤维蛋白肽“MFibBi”，将用于离体“武装”巨噬细胞群，以便在小鼠尾部损伤模型中给药。假设：双特异性抗体将巨噬细胞靶向伤口将加速伤口愈合。具体目标： 1) 生成并验证MFiBi。 2) 表征细胞因子成熟的巨噬细胞群。 3) 使用 MFiBi 将巨噬细胞靶向实验诱导的伤口。