Studies of plant produced Immune checkpoint inhibitors as a potential immunotherapeutic antibody

Green, Antibody-producing Machines

A plant-based monoclonal antibody goes head-to-head with its commercial counterpart to target tumours in mice

Immune checkpoint inhibitors – a promising treatment with a prohibitive price tag

Immune checkpoint inhibitors (ICIs) are a well-known class of immunotherapeutic drugs that have emerged in the past 10 years as an effective treatment option for several cancers. The therapy targets immune checkpoints, key regulators of the immune system that when stimulated can dampen the immune response to an immunologic stimulus.

However, recombinant proteins such as ICIs for human use are prohibitively expensive due to the high cost of manufacturing. As such, the affordability of cancer care and biologics has always been a major concern, particularly in underdeveloped nations where drug prices limit access to adequate healthcare and cancer treatment.

Plants take the stage as potential ‘protein factories’

In this article published in Nature (August 2023)[1] researchers present merits of plant expression systems, in terms of rapid scalability and relative cost efficiency, for synthesising complex glycoproteins.

The production and economic advantages of plants underlie their potential as competent pharmaceutical factories. Plant cells, tissues, and whole plants are among the primary systems used to manufacture therapeutic recombinant proteins for commercial, industrial, or pharmaceutical applications.

Case study: comparing a plant-produced protein with the commercial standard

The article presented findings based on the production of Atezolizumab (the first ICI antibody to target immune checkpoint PD-L1 and approved for treating bladder cancer) produced in the plant Nicotiana benthamiana, an indigenous Australian plant and a close relative of tobacco. demonstrating high expression levels within 4–6 days post-infiltration. The study showed the plant-produced Atezolizumab:

• had comparable antigen-binding affinities to human PD-L1 in vitro to the commercial Atezolizumab (Tecentriq)
• was as effective as Tecentriq in inhibiting tumour growth in vivo (tumour-bearing mice).

These findings confirm the plant’s ability to serve as an efficient production platform for Atezolizumab and suggested that it could be used to alleviate the cost of production of existing anticancer products, such as ICIs, and increase patient access to these cancer treatments.

[1] K Rattanapisit, CJI Bulaon, R Strasser, H Sun and W Phoolcharoen, ‘In vitro and in vivo studies of plant-produced Atezolizumab as a potential immunotherapeutic antibody’, Sci Rep 13, 14146 (2023). doi: https://doi.org/10.1038/s41598-023-41510-w.