Enhancing effect of low culture temperature on specific antibody productivity of recombinant Chinese hamster ovary cells: Clonal variation

Abstract

To understand the different responses of recombinant Chinese hamster ovary (rCHO) cells to low culture temperature regarding specific productivity (q), 12 parental clones and their corresponding amplified clones producing a humanized antibody were cultivated at 32 and 37 degreesC. The specific growth rate of all clones, including both parental and amplified clones, decreased by 30-63% at 32 degreesC, compared to rates at 37degreesC. In contrast, their specific antibody productivity (q(Ab)) was significantly enhanced at 32 degreesC. Furthermore, the degree of q(Ab) enhancement at 32 degreesC varied a lot from 4- to 25-fold among the parental clones. At 32 degreesC, most of the amplified clones, regardless of methotrexate (MTX) levels, also showed enhanced q(Ab) but to a lesser extent than their parental clones. However, clone 14 amplified at 0.32 muM MTX (clone 14-0.32) and clone 20 amplified at 1 muM MTX (clone 20-1.00), unlike their parental clones, did not show enhanced q(Ab) at 32 degreesC. Thus, it was found that the enhancing effect of low culture temperature on q of rCHO cells depends on clones. Taken together, the results obtained here emphasize the importance of clonal selection for the successful application of low culture temperature to the enhanced foreign protein production in rCHO cells.