Obinutuzumab a Promising Candidate for Plant-Produced Biosimilar

Researchers based in the Republic of Korea have published data suggesting that they were able to produce a promising biosimilar obinutuzumab candidate from the plant Nicotiana benthamiana L. that is equivalent to obinutuzumab produced in glyco-engineered Chinese hamster ovary (CHO) cells (CHO-obinutuzumab). Obinutuzumab (Gazyva) is Genentech’s monoclonal antibody treatment for chronic lymphocytic leukemia, which works by depleting CD20-expressing lymphoma cells and B cells.

Obinutuzumab is a so-called “biobetter,” a therapy that has resulted from intentionally altering an existing biologic product in order to improve its clinical effects, require less frequent administration, or enhance tolerability. Obinutuzumab is a biobetter of rituximab (which has a different method of action) has been shown to be less immunogenic and to trigger greater cytotoxicity than rituximab. Obinutuzumab is currently considered the best treatment for non-Hodgkin lymphoma, the authors note.

The cost of producing monoclonal antibodies for anti-cancer immunotherapy is high, and the protein production system in plants has been shown to be a cost-efficient and easy-to-scale-up platform for generating biologic drugs. In addition to being cost-efficient, the use of plants for protein production completely eliminates the risks of virus or residual protein contamination that is associated with mammalian production systems, the researchers note. A more economical and mammalian protein risk-free production platform is in high demand for the entire biopharmaceutical industry, so a plant-based protein-production platform is a promising approach that may contribute to patients’ well-being globally if it results in less-costly drugs.

The study demonstrated that the 2 forms of plant-obinutuzumab generated can be used to kill CD20-expressing lymphoma cells just by direct binding without complements or effector cells, similar to CHO-obinutuzumab.

N. benthamiana is the most widely used experimental host in plant virology, and is susceptible to a wide variety of other plant-pathogenic agents, such as bacteria, making N. benthamiana a cornerstone of host-pathogen research that is also rapidly gaining popularity in studies of protein expression and purification.

The researchers said their study demonstrated that obinutuzumab is a promising candidate as a plant-produced monoclonal antibody because they showed that plant-obinutuzumab has an equivalent ability to bind CD20 and causes direct binding-mediated B-cell death compared to CHO-obinutuzumab.

While there have been no reports of human studies that show plant-derived proteins are more immunogenic than mammalian-derived biotherapeutics, careful observation of the progress toward the use of plant-derived proteins is nevertheless needed for more efficient and rational development of plant-produced bio-drugs.