EFFECT OF CULTURE CONDITIONS ON IGM ANTIBODY STRUCTURE, PHARMACOKINETICS AND ACTIVITY

被引：64

作者：

MAIORELLA, BL ^{[1
]}

WINKELHAKE, J ^{[1
]}

YOUNG, J ^{[1
]}

MOYER, B ^{[1
]}

BAUER, R ^{[1
]}

HORA, M ^{[1
]}

ANDYA, J ^{[1
]}

THOMSON, J ^{[1
]}

PATEL, T ^{[1
]}

PAREKH, R ^{[1
]}

机构：

[1] OXFORD GLYCOSYST LTD,OXFORD OX14 1RG,ENGLAND

来源：

BIO-TECHNOLOGY | 1993年 / 11卷 / 03期

关键词：

D O I：

10.1038/nbt0393-387

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

Culture conditions affect the binding activity, charge heterogeneity, conformational stability, glycosylation, and pharmacokinetics of human monoclonal IgM HMAB-10058. The 10058 human/human/murine trioma was grown in serum-free airlift suspension culture, hollow fiber perfusion culture, or in nude mouse ascites. The ascites-produced antibody showed reduced conformational stability, greater charge and glycoform heterogeneity, and a lower average degree of sialylation than the in vitro culture-produced material. Mean residence time after IV injection in rats was approximately 80-fold greater for the ascites culture-produced material, but specific binding activity was less than 5% of that for the airlift-produced material. In vitro culture in serum-supplemented media (in a hollow fiber perfusion reactor or in shake-flasks) resulted in antibody with pharmacokinetics intermediate between the serum-free airlift and ascites-produced materials. Incubation of airlift-produced antibody in ascites fluid also resulted in material with intermediate pharmacokinetics. Conclusions regarding the effect of culture conditions on antibody product cannot be generalized, as in vitro-produced antibody derived from two related cell lines (HMAB-10233 and HMAB-10390) had long mean residence times similar to that of ascites-produced HMAB-10058.

引用

页码：387 / 392

页数：6

共 35 条

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