Wawrzynczak E J, Cumber A J, Parnell G D, Jones P T, Winter G
Drug Targeting Laboratory, Section of Medicine, Institute of Cancer Research, Sutton, Surrey, U.K.
Mol Immunol. 1992 Feb;29(2):213-20. doi: 10.1016/0161-5890(92)90102-4.
The serum half-lives of a wild-type recombinant mouse monoclonal antibody of the IgG2b isotype and a mutant antibody differing from the wild-type antibody by a single amino acid substitution introduced into the CH2 domain, the replacement of Asn 297 by Ala to delete the conserved site of heavy chain glycosylation, were determined in the rat. The biological half-life of the aglycosyl Asn 297-Ala mutant recombinant antibody (4.8 days) was significantly shorter than that of the normally glycosylated wild-type antibody (7.4 days) by enzyme immunoassay. A similar difference between the biological half-lives of 125I-labelled aglycosyl and wild-type antibodies (2.9 and 4.0 days, respectively) was determined by gamma counting. Analysis of serum samples demonstrated that both recombinant antibodies were present in the circulation predominantly as intact monomeric IgG and revealed no differences that could account for the more rapid elimination of the aglycosyl antibody. The results of this investigation indicate that the carbohydrate residues contribute only in part to the survival of IgG in vivo and suggest that the diminished half-life of the aglycosyl antibody is due to increased catabolism in the extravascular tissues.
在大鼠体内测定了IgG2b同种型野生型重组小鼠单克隆抗体以及一种突变抗体的血清半衰期。该突变抗体与野生型抗体的区别在于，其CH2结构域中有一个氨基酸被替换，即将Asn 297替换为Ala，从而删除了重链糖基化的保守位点。通过酶免疫测定法发现，无糖基化Asn 297-Ala突变重组抗体的生物半衰期（4.8天）明显短于正常糖基化野生型抗体的生物半衰期（7.4天）。通过γ计数法测定，125I标记的无糖基化抗体和野生型抗体的生物半衰期也存在类似差异（分别为2.9天和4.0天）。血清样本分析表明，两种重组抗体在循环中主要以完整的单体IgG形式存在，且未发现任何差异可以解释无糖基化抗体消除更快的原因。这项研究结果表明，碳水化合物残基仅部分有助于IgG在体内的存活，并提示无糖基化抗体半衰期缩短是由于血管外组织中分解代谢增加所致。
