Monoclonal antibodies (are laboratory-designed proteins that mimic the immune system’s antibodies and these are important for the treatment of cancer and autoimmune diseases. Such lab-designed monoclonal antibodies, mimicking the immune system, therefore play a pivotal role in treating diseases.
In a new study published in the Journal of Biotechnology, researchers from Tokyo University of Science, Japan, have unveiled a novel approach to enhance the efficacy of monoclonal antibodies by manipulating polyamines.
This development opens avenues for stable antibody production, potential cost reduction, and improved quality control. Each of these steps could help to trigger significant advancements in biopharmaceutical manufacturing. Cell lines such as the Chinese hamster ovary (CHO) cells are generally used to produce monoclonal antibodies.
One of the challenges in pharmaceutical production is with achieving consistent manufacturing and production of monoclonal antibodies. In particular, their functional profiles depend on cell culture conditions.
The new research has been conducted on the role of intracellular polyamines on N-glycan profiles of monoclonal antibodies. The research has found that polyamine depletion led to stress response in cells, leading to an increase in galactosylation of the monoclonal antibodies.
Polyamines are present in millimolar concentrations in all living organisms and play essential roles in normal cell growth and differentiation. The CHO cells used to produce monoclonal antibodies lack arginase activity to produce polyamines in serum-free media. This means there is a decrease in intracellular polyamine levels, which causes a low growth rate and cell viability during long-term cultivation.
This is important since the composition of N-linked glycans affects the overall therapeutic efficacy, targeting ability, and immune-specificity of these antibodies. This means it is necessary for scientists to meticulously regulate N-linked glycan profiles throughout the manufacturing process. Otherwise, the heterogeneity of the N-linked glycan profile of monoclonal antibodies becomes more affected by the cell culture duration and changes in nucleotide sugars and glycosylation enzyme levels.
To counter this, the researchers demonstrated that supplementation of spermidine recovered N-glycan profiles.
These findings should contribute to the stable production of antibody-based drugs.
The research is titled “Intracellular polyamine depletion induces N-linked galactosylation of the monoclonal antibody produced by CHO DP-12 cells.”
