Abstract
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.
Highlights
Immunotherapy is currently a promising cancer treatment that activates the immune system and alleviates the suppression of the immune system by the tumour
The reducing gel electrophoresis confirmed that the heavy chain (HC) and light chain (LC) of anti-PD1 monoclonal antibody (mAb) were expressed in leaves with the expected molecular weights (Fig. 1D)
The result confirmed that the purified plant-produced monoclonal antibody remains monomer as commercial nivolumab (Fig. 1G)
Summary
Immunotherapy is currently a promising cancer treatment that activates the immune system and alleviates the suppression of the immune system by the tumour. Comparing to current antibody production platforms, plants offer several advantages for producing antibodies over others. Plant-produced recombinant proteins were shown to meet the same good manufacturing practice criteria as proteins produced in mammalian cells, such as appearance, stability, half-life, immunogenicity etc[9]. These advantages for plant platforms suggest that they represent an attractive alternative for producing biopharmaceuticals for developing countries[10,11]. We further developed an anti-PD1 monoclonal antibody (mAb), nivolumab, as a possible cancer immunotherapeutic by applying plant technology that enables cost-effective and scalable antibody production. This study is the first to demonstrate the use of plant-derived mAb for cancer immunotherapy
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