COMBODY: one‐domain antibody multimer with improved avidity
COMBODY: one‐domain antibody multimer with improved avidity
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DOI：
10.1038/icb.2010.21
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发表时间：
2010-08
影响因子：
4
通讯作者：
Xuekai Zhu;Lei Wang;Rongzhi Liu;B. Flutter;Shenghua Li;Jie Ding;Hua Tao;ChangZhen Liu;Meiyi Sun;Bin Gao
中科院分区：
文献类型：
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作者：
Xuekai Zhu;Lei Wang;Rongzhi Liu;B. Flutter;Shenghua Li;Jie Ding;Hua Tao;ChangZhen Liu;Meiyi Sun;Bin Gao
抗体（Abs）已被工程化为小的抗原结合片段并重建成多价高亲合力分子，以改善体内药理学和临床使用的功效。为了增加对HLA-A2复合物具有特异性的T细胞受体样单域抗体（sdAb）的亲合力，我们将sdAb融合到来自人软骨寡聚基质蛋白（COMP 48）的卷曲螺旋肽，以制备sdAb多聚体，称为combody。该复合体显著提高了sdAb的亲合力，同时保留了对靶细胞的特异性。该策略还被扩展为通过将sdAb融合至COMP 48的N末端并将抗CD 3单链可变片段融合至COMP 48的C末端来产生双特异性复合体。双特异性复合体能够有效地介导对靶细胞的体外细胞毒性。因此，可以广泛采用复合抗体的制备策略，以提高抗体片段的亲合力，为进一步的应用奠定基础。
Antibodies (Abs) have been engineered into small antigen‐binding fragments and rebuilt into multivalent high‐avidity molecules for improvingin vivopharmacokinetics and efficacy in clinical use. To increase the avidity of a T‐cell receptor‐like single‐domain Ab (sdAb) specific for HLA‐A2 complex, we fused the sdAb to a coiled‐coil peptide derived from human cartilage oligomeric matrix protein (COMP48) to make an sdAb multimer, termed combody. The combody improved the binding avidity of sdAb significantly, whereas the specificity for the targeted cells was retained. The strategy was also expanded to create a bispecific combody by fusing an sdAb to the N‐terminal and an anti‐CD3 single‐chain variable fragment to the C‐terminal of COMP48. The dual‐specific combody was able to efficiently mediate cytotoxicity against the target cellsin vitro. Taken together, the strategy to make combody could be widely adopted to increase the avidity of Ab fragment for further application.