Comparison of Antibody Molecules Produced from Two Cell Lines with Contrasting Productivities and Aggregate Contents

被引：13

作者：

Ishii, Yoichi ^{[1
,3
]}

Imamoto, Yasufumi ^{[1
]}

Yamamoto, Rie ^{[1
]}

Tsukahara, Masayoshi ^{[2
]}

Wakamatsu, Kaori ^{[3
]}

机构：

[1] Kyowa Hakko Kirin Co Ltd, Bioproc Res & Dev Labs, Takasaki, Gunma 3700013, Japan

[2] Kyowa Hakko Kirin Co Ltd, Chiyoda Ku, Tokyo 1008185, Japan

[3] Gunma Univ, Grad Sch Engn, Kiryu, Gunma 3768515, Japan

来源：

BIOLOGICAL & PHARMACEUTICAL BULLETIN | 2015年 / 38卷 / 02期

关键词：

antibody aggregate; light chain production; cell line; antibody fragment; covalent aggregate; non-covalent aggregate; HAMSTER OVARY CELLS; PROTEIN AGGREGATION; MONOCLONAL-ANTIBODIES; RECOMBINANT ANTIBODY; FRAGMENTATION; MECHANISMS; HETEROGENEITY; STABILITY; CULTURE; QUALITY;

D O I：

10.1248/bpb.b14-00729

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Cell culture processes that produce therapeutic antibodies with high productivity (titer) and low aggregate content reduce the risk of adverse effects and expense to patients. To elucidate the mechanism of aggregate formation, we compared trastuzumab samples produced from two contrasting cell lines: cell line A, which exhibits high titer and low aggregate content, and cell line B, which exhibits low titer and high aggregate content. Cell line B produced significantly fewer (approximately 1/3) antibodies compared with cell line A and contained higher (approximately 3-fold) percentages of aggregates. The aggregates of antibodies found in the protein A-purified samples of cell line B were associated mostly with noncovalent interactions. Cell line B exhibited a low content of monomers/dimers of light chains in the medium and within cells. Because light chains are essential for the correct folding of heavy chains and secretion of mature antibodies, the characteristics of cell line B may be attributed to low levels of light chain production. In addition, protein A-purified antibodies from cell line B (but not those from cell line A) contained fragments that are expected to expose the hydrophobic C(H)3 domain, which may serve as nuclei for aggregation.

引用

页码：306 / 316

页数：11

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