Victoria Argentova*, Teimur Aliev, Dmitry Dolgikh and Mikhail Kirpichnikov Pages 990 - 996 ( 7 )
Background: Immunoglobulin (Ig) G is the most commonly used therapeutic antibodies. Recently, the interest in IgA antibodies to treat respiratory infectious diseases has been increasing. The reason for the inefficient use of IgA is recombinant antibody aggregation in cell culture, affecting the longevity and productivity of cell lines. Lactate is an important metabolite that affects the cultivation of stable cell lines producing monoclonal antibodies.Methods: In the present study, we investigated whether different combinations of succinic acid and micro-additives affect lactate production, which correlates with productivity. The effect of succinic acid substitution on productivity of cells producing IgG/IgA was analyzed using the static culture method in a six-well plate. Lactate was measured in supernatant of cell culture indirectly by using the activity of lactate dehydrogenase (LDH).A low lactate level was observed in cultivation medium supplemented with succinic acid or asparagine combined with some inorganic salts. Results: The results also demonstrated the effect of component supplementation on homogeneity, longevity, and productivity of cell culture. Supplementation of succinic acid eliminated cell aggregation and improved homogeneity of stable cell lines producing IgG and, especially, IgA. Conclusion: Overall, succinic acid supplementation to the culture medium has potential biotechnological applications in the production IgG and IgA.
IgG, IgA, lactate, monoclonal antibody, productivity, succinic acid.
Department of Bioengineering, School of Biology, Lomonosov Moscow State University, Leninskiye Gory 1-12, Moscow, 119234, Department of Chemical Enzymology, School of Chemistry, Lomonosov Moscow State University, Leninskiye Gory 1-3, Moscow, 119234, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya ul 16/10, GSP-7, Moscow, 117997, Department of Bioengineering, School of Biology, Lomonosov Moscow State University, Leninskiye Gory 1-12, Moscow, 119234