Engineering therapeutic antibodies for improved function

被引：46

作者：

Presta, LG ^{[1
]}

Shields, RL ^{[1
]}

Namenuk, AK ^{[1
]}

Hong, K ^{[1
]}

Meng, YG ^{[1
]}

机构：

[1] Genentech Inc, San Francisco, CA 94080 USA

来源：

BIOCHEMICAL SOCIETY TRANSACTIONS | 2002年 / 30卷

关键词：

antibody; antibody-dependent cellular cytotoxicity (ADCC); Fc receptor; neonatal Fc receptor (FcRn);

D O I：

10.1042/bst0300487

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The binding sites on human IgG1 for human Fcgamma receptor (FcgammaR) 1, FcgammaRIIa, FcgammaRIIb, FcgammaRIIIa and neonatal FcR have been mapped. A common set of IgG1 residues is involved in binding to all FcgammaRs, while FcgammaRII and FcgammaRIII utilize distinct sites outside this common set. In addition to residues which abrogated binding to the FcgammaR, several positions were found which improved binding only to specific FcgammaRs or simultaneously improved binding to one type of FcgammaR and reduced binding to another type. Selected IgG1 variants with improved binding to FcgammaRIIIa were then tested in an in vitro antibody-dependent cellular cytotoxicity (ADCC) assay and showed an enhancement in ADCC when either peripheral blood mononuclear cells or natural killer cells were used.

引用

页码：487 / 490

页数：4

共 40 条

[1] Targeted anti-cancer therapy using rituximab, a chimaeric anti-CD20 antibody (IDEC-C2B8) in the treatment of non-Hodgkin's B-cell lymphoma [J].