Plant-Produced Pharmaceuticals Research Unit, Chulalongkorn University, 254 Phyathai Road, Patumwan, Bangkok, 10330, Thailand.
Pharmacognosy and Pharmaceutical Botany Department, Faculty of Pharmaceutical Sciences, Chulalongkorn University, 254 Phyathai Road, Patumwan, Bangkok, 10330, Thailand.
Sci Rep. 2019 Oct 23;9(1):15205. doi: 10.1038/s41598-019-51656-1.
Immunotherapy has emerged as a promising and effective treatment for cancer. The frequently used immunotherapy agents are immune checkpoint inhibitors, such as antibodies specific to PD1, PD-L1, or CTLA-4. However, these drugs are highly expensive, and most people in the world cannot access the treatment. The development of recombinant protein production platforms that are cost-effective, scalable, and safe is needed. Plant platforms are attractive because of their low production cost, speed, scalability, lack of human and animal pathogens, and post-translational modifications that enable them to produce effective monoclonal antibodies. In this study, an anti-PD1 IgG4 monoclonal antibody (mAb) was transiently produced in Nicotiana benthamiana leaves. The plant-produced anti-PD1 mAb was compared to the commercial nivolumab produced in CHO cells. Our results showed that both antibodies have similar protein structures, and the N-glycans on the plant-produced antibody lacks plant-specific structures. The PD1 binding affinity of the plant-produced and commercial nivolumab, determined by two different techniques, that is, enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR), are also comparable. Plant-produced nivolumab binds to human PD1 protein with high affinity and specificity, blocks the PD-1/PD-L1 interaction, and enhances T cell function, comparable to commercial nivolumab. These results confirmed that plant-produced anti-PD1 antibody has the potential to be effective agent for cancer immunotherapy.
免疫疗法已成为癌症治疗的一种有前途且有效的方法。常用的免疫治疗药物是免疫检查点抑制剂，例如针对 PD1、PD-L1 或 CTLA-4 的抗体。然而，这些药物非常昂贵，世界上大多数人无法获得这种治疗。因此，需要开发具有成本效益、可扩展且安全的重组蛋白生产平台。植物平台因其低成本、快速、可扩展、缺乏人类和动物病原体以及能够产生有效单克隆抗体的翻译后修饰而具有吸引力。在这项研究中，在烟草叶片中瞬时生产了抗 PD1 IgG4 单克隆抗体 (mAb)。将植物产生的抗 PD1 mAb 与在 CHO 细胞中生产的商业 nivolumab 进行了比较。我们的结果表明，两种抗体具有相似的蛋白质结构，并且植物产生的抗体上的 N-聚糖缺乏植物特异性结构。通过两种不同的技术，即酶联免疫吸附测定 (ELISA) 和表面等离子体共振 (SPR)，确定了植物产生的和商业 nivolumab 的 PD1 结合亲和力也相当。植物产生的 nivolumab 与人 PD1 蛋白具有高亲和力和特异性结合，阻断 PD-1/PD-L1 相互作用，并增强 T 细胞功能，与商业 nivolumab 相当。这些结果证实，植物产生的抗 PD1 抗体有可能成为癌症免疫治疗的有效药物。
