From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice
From XenoMouse technology to panitumumab, the first fully human antibody product from transgenic mice
复制标题
DOI：
10.1038/nbt1337
复制
发表时间：
2007-10-01
影响因子：
46.9
通讯作者：
Schwab, Gisela
中科院分区：
文献类型：
--
作者：
Jakobovits, Aya;Amad, Rafael G.;Schwab, Gisela
由于小鼠序列在人体中的免疫原性，治疗性单克隆抗体显示出有限的功效和安全性。在克服这些障碍的方法中，有一种是通过基因工程改造具有“人源化”体液免疫系统的转基因小鼠。一种这样的转基因系统，XenoMouse，通过将几乎整个人免疫球蛋白基因座引入具有失活的小鼠抗体机制的小鼠的生殖系中，成功地再现了小鼠中的人抗体应答。XenoMouse品系已用于产生针对多种疾病适应症中的靶点的许多高亲和力、全人源抗体，其中许多抗体正在临床开发中取得进展。然而，该技术的验证一直在等待帕尼单抗（Vectibix）最近的监管批准，帕尼单抗是一种针对表皮生长因子受体（EGFR）的全人抗体，可用于治疗晚期结直肠癌。帕尼单抗的成功开发代表了人类体液免疫系统改造小鼠及其未来应用的里程碑。
Therapeutic monoclonal antibodies have shown limited efficacy and safety owing to immunogenicity of mouse sequences in humans. Among the approaches developed to overcome these hurdles were transgenic mice genetically engineered with a 'humanized' humoral immune system. One such transgenic system, the XenoMouse, has succeeded in recapitulating the human antibody response in mice, by introducing nearly the entire human immunoglobulin loci into the germ line of mice with inactivated mouse antibody machinery. XenoMouse strains have been used to generate numerous high-affinity, fully human antibodies to targets in multiple disease indications, many of which are progressing in clinical development. However, validation of the technology has awaited the recent regulatory approval of panitumumab (Vectibix), a fully human antibody directed against epidermal growth factor receptor (EGFR), as treatment for people with advanced colorectal cancer. The successful development of panitumumab represents a milestone for mice engineered with a human humoral immune system and their future applications.