In vitro and in vivo studies of plant-produced Atezolizumab as a potential immunotherapeutic antibody

植物生产的阿特珠单抗作为潜在免疫治疗抗体的体外和体内研究

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作者:Kaewta Rattanapisit, Christine Joy I Bulaon, Richard Strasser, Hongyan Sun, Waranyoo Phoolcharoen

Abstract

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.

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