Marasco Wayne A, Sui Jianhua
Department of Cancer Immunology & AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School 44, Binney Street, Boston, Massachusetts 02115, USA.
Nat Biotechnol. 2007 Dec;25(12):1421-34. doi: 10.1038/nbt1363.
Monoclonal antibodies (mAbs) have long provided powerful research tools for virologists to understand the mechanisms of virus entry into host cells and of antiviral immunity. Even so, commercial development of human (or humanized) mAbs for the prophylaxis, preemptive and acute treatment of viral infections has been slow. This is surprising, as new antibody discovery tools have increased the speed and precision with which potent neutralizing human antiviral mAbs can be identified. As longstanding barriers to antiviral mAb development, such as antigenic variability of circulating viral strains and the ability of viruses to undergo neutralization escape, are being overcome, deeper insight into the mechanisms of mAb action and engineering of effector functions are also improving the efficacy of antiviral mAbs. These successes, in both industrial and academic laboratories, coupled with ongoing changes in the biomedical and regulatory environments, herald an era when the commercial development of human antiviral mAb therapies will likely surge.
长期以来,单克隆抗体(mAb)一直为病毒学家提供强大的研究工具,以了解病毒进入宿主细胞的机制和抗病毒免疫机制。即便如此,用于预防、抢先治疗和急性治疗病毒感染的人源(或人源化)单克隆抗体的商业开发进展缓慢。这令人惊讶,因为新的抗体发现工具提高了识别强效中和性人源抗病毒单克隆抗体的速度和精度。随着抗病毒单克隆抗体开发的长期障碍,如循环病毒株的抗原变异性和病毒产生中和逃逸的能力,正在被克服,对单克隆抗体作用机制的更深入了解和效应功能的工程化也在提高抗病毒单克隆抗体的疗效。工业和学术实验室的这些成功,再加上生物医学和监管环境的持续变化,预示着一个人源抗病毒单克隆抗体疗法商业开发可能会蓬勃发展的时代。