BiStro Biotech Consulting, Bridgewater, NJ, 08807, USA.
Protein Cell. 2018 Jan;9(1):86-120. doi: 10.1007/s13238-017-0457-8. Epub 2017 Aug 18.
As of May 1, 2017, 74 antibody-based molecules have been approved by a regulatory authority in a major market. Additionally, there are 70 and 575 antibody-based molecules in phase III and phase I/II clinical trials, respectively. These total 719 antibody-based clinical stage molecules include 493 naked IgGs, 87 antibody-drug conjugates, 61 bispecific antibodies, 37 total Fc fusion proteins, 17 radioimmunoglobulins, 13 antibody fragments, and 11 immunocytokines. New uses for these antibodies are being discovered each year. For oncology, many of the exciting new approaches involve antibody modulation of T-cells. There are over 80 antibodies in clinical trials targeting T cell checkpoints, 26 T-cell-redirected bispecific antibodies, and 145 chimeric antigen receptor (CAR) cell-based candidates (all currently in phase I or II clinical trials), totaling more than 250 T cell interacting clinical stage antibody-based candidates. Finally, significant progress has been made recently on routes of delivery, including delivery of proteins across the blood-brain barrier, oral delivery to the gut, delivery to the cellular cytosol, and gene- and viral-based delivery of antibodies. Thus, there are currently at least 864 antibody-based clinical stage molecules or cells, with incredible diversity in how they are constructed and what activities they impart. These are followed by a next wave of novel molecules, approaches, and new methods and routes of delivery, demonstrating that the field of antibody-based biologics is very innovative and diverse in its approaches to fulfill their promise to treat unmet medical needs.
截至 2017 年 5 月 1 日，已有 74 种基于抗体的分子在一个主要市场的监管机构获得批准。此外，还有 70 种和 575 种处于 III 期和 I/II 期临床试验阶段的基于抗体的分子。这些总计 719 种处于临床阶段的基于抗体的分子包括 493 种裸 IgG、87 种抗体药物偶联物、61 种双特异性抗体、37 种全 Fc 融合蛋白、17 种放射免疫球蛋白、13 种抗体片段和 11 种免疫细胞因子。每年都有新的用途被发现。在肿瘤学领域，许多令人兴奋的新方法涉及抗体对 T 细胞的调节。有超过 80 种临床试验中针对 T 细胞检查点的抗体，26 种 T 细胞重定向双特异性抗体，和 145 种嵌合抗原受体（CAR）基于细胞的候选物（所有目前都处于 I 期或 II 期临床试验），总数超过 250 种 T 细胞相互作用的临床阶段基于抗体的候选物。最后，最近在给药途径方面取得了重大进展，包括将蛋白质递送到血脑屏障，口服递送到肠道，递送到细胞胞质溶胶，以及基于基因和病毒的抗体传递。因此，目前至少有 864 种处于临床阶段的基于抗体的分子或细胞，它们的构建方式和赋予的活性具有令人难以置信的多样性。接下来是一波新的分子、方法和新的给药途径和方法，这表明基于抗体的生物制剂领域在其方法上非常具有创新性和多样性，以实现其治疗未满足的医疗需求的承诺。
