The improved technology of HER2-specific monoclonal antibody production in plantsтезисы доклада Тезисы

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[1] The improved technology of her2-specific monoclonal antibody production in plants / E. V. Sheshukova, T. V. Komarova, E. N. Kosobokova et al. // FEBS Open Bio. — Vol. 8 of Supplement 1. — FEBS Open Bio Prague, Czech Republic, 2018. — P. 173–173. Similar to animal cells, plant cells possess mechanisms for protein synthesis and post-translational modifications that are considered to be factories for monoclonal antibody production. Using a transient expression system, we previously developed a technology for the production of the HER2-specific monoclonal antibodies trastuzumab plant biosimilar (TPB) and pertuzumab plant biosimilar (PPB); their anti-cancer activity in animal models is not inferior to the original therapeutic monoclonal antibodies. Here, we suggest two ways to improve this technology. The first method involves the creation of bispecific antibodies that combine the properties of TPB and PPB (Bi-T/P_PB). To this end, we used several approaches to create Bi-T/P_PB. The resulting antibodies differed in stability and output but invariably demonstrated a high level of anti-cancer activity. The second approach to improving the technology is based on the novel transcriptional promoter of the Kunitz peptidase inhibitor (proKPI) that we have isolated. This promoter effectively directed the expression of genes encoding the TPB light and heavy chains in plant cells. Moreover, we created the proKPI-based vector that encodes the fusion protein consisting of TPB light and heavy chains joined by a 33-aa linker (KP6pp), which is recognized by the N. benthamiana endogenous kex2p-like protease. The processed TPB (pTPB) variant showed a high level of anti-cancer activity but also contained a small fraction of the unprocessed form of the polypeptide. The increased level of endogenous kex2p-like protease could result in more effective processing of the pTPB polypeptide. Therefore, we isolated the gene encoding the endogenous kex2p-like N. benthamiana protease to allow its overexpression using a transient expression system. We are confident that improving the technology of producing monoclonal antibody plant biosimilars will make them attractive for cancer therapy because of their economic benefits and high production rates. This study was performed with financial support from the Russian Science Foundation (project No. 16-14-00002). [ DOI ]

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