Baiya Phytopharm Co., Ltd., Bangkok, Thailand.
Center of Excellence in Plant-Produced Pharmaceuticals, Chulalongkorn University, Bangkok, 10330, Thailand.
Sci Rep. 2023 Aug 29;13(1):14146. doi: 10.1038/s41598-023-41510-w.
Immune checkpoint inhibitors are a well-known class of immunotherapeutic drugs that have been used for effective treatment of several cancers. Atezolizumab (Tecentriq) was the first antibody to target immune checkpoint PD-L1 and is now among the most commonly used anticancer therapies. However, this anti-PD-L1 antibody is produced in mammalian cells with high manufacturing costs, limiting cancer patients' access to the antibody treatment. Plant expression system is another platform that can be utilized, as they can synthesize complex glycoproteins, are rapidly scalable, and relatively cost-efficient. Herein, Atezolizumab was transiently produced in Nicotiana benthamiana and demonstrated high expression level within 4-6 days post-infiltration. After purification by affinity chromatography, the purified plant-produced Atezolizumab was compared to Tecentriq and showed the absence of glycosylation. Furthermore, the plant-produced Atezolizumab could bind to PD-L1 with comparable affinity to Tecentriq in ELISA. The tumor growth inhibitory activity of plant-produced Atezolizumab in mice was also found to be similar to that of Tecentriq. These findings confirm the plant's capability to serve as an efficient production platform for immunotherapeutic antibodies and suggest that it could be used to alleviate the cost of existing anticancer products.
免疫检查点抑制剂是一类众所周知的免疫治疗药物,已被用于有效治疗多种癌症。阿替利珠单抗(Tecentriq)是首个针对免疫检查点 PD-L1 的抗体,现已成为最常用的抗癌疗法之一。然而,这种抗 PD-L1 抗体是在哺乳动物细胞中生产的,制造成本高,限制了癌症患者获得抗体治疗的机会。植物表达系统是另一个可利用的平台,因为它们可以合成复杂的糖蛋白,可快速扩展规模,且相对具有成本效益。在此,阿替利珠单抗在本氏烟中瞬时表达,在侵染后 4-6 天内即可达到高表达水平。通过亲和层析纯化后,与 Tecentriq 相比,纯化的植物源性阿替利珠单抗显示出无糖基化的特征。此外,在 ELISA 中,植物源性阿替利珠单抗与 PD-L1 的结合亲和力与 Tecentriq 相当。在小鼠中的肿瘤生长抑制活性研究也表明,植物源性阿替利珠单抗的效果与 Tecentriq 相似。这些发现证实了植物作为免疫治疗性抗体高效生产平台的能力,并表明它可以用于减轻现有抗癌产品的成本。