Genome-Wide Analysis of Mouse Myeloma Cell Lines Expressing Therapeutic Antibodies

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Abstract

Manufacturing cell line development involves transfection of therapeutic antibody genes into host cell lines and isolation of primary transfectomas that upon subcloning yield high expressing cell lines secreting the desired antibody. In an attempt to increase productivity of these cell lines, we set out to identify cellular genes whose expression level may affect antibody productivity. For this purpose, three different sets of mouse myeloma production cell lines expressing variable levels of three different therapeutic antibodies were subjected to microarray analysis using Murine GeneChip MG_U74Av2 arrays. A total of 456 genes were identified showing significant differential expression between at least one high expresser versus the control or its corresponding low expresser. Among these, 161 genes were common among at least one set of cell lines, and 26 genes were common among two or more sets of cell lines. Functional classification revealed that a majority of these genes have biological process function related to cell metabolism and cell growth. A subset of the 26 genes that were identified as commonly regulated among any two or all three sets of cell lines were selected (by several criteria) for quantitative PCR confirmation of the microarray methodology. The expression level of two genes, Secretory Leukocyte Protease Inhibitor (SLPI) and Cell Division Cycle-6 (Cdc6), correlated with antibody productivity in at least two sets of cell lines, suggesting that they can potentially be utilized as targets for engineering a superior transfection host cell line. Additionally, these genes may be used for screening murine myeloma production cell lines for superior productivity.

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