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抗人CD34單克隆抗體(QBEND/10)之蛋白質從頭測序、人源化以及其體外應用效果
Dissertation

抗人CD34單克隆抗體(QBEND/10)之蛋白質從頭測序、人源化以及其體外應用效果

Fan, Chia Yu
Doctor of Philosophy (PHD), 國立清華大學, 生物資訊與結構生物研究所
2016

Abstract

單株抗體 從頭測序 人源化 CD34 抑制血管新生治療 Monoclonal antibody De novo sequencing Humanization CD34 Antiangiogenic therapy
QBEND/10 is a mouse immunoglobulin gamma 1 heavy chain and lambda light chain monoclonal antibody with strict specificity against human hematopoietic progenitor cell antigen CD34. In vitro study showed that QBEND/10 impaired tube formation of human umbilical vein endothelial cells (HUVECs), suggesting that the antibody may be of potential benefit in blocking tumor angiogenesis. We provided a de novo protein sequencing method through tandem mass spectrometry to identify amino acid sequences in variable heavy and light chains of QBEND/10. To reduce immunogenicity for clinical applications, QBEND/10 was further humanized using resurfacing approach. We demonstrate that the de novo sequenced and humanized QBEND/10 retains biological functions of the parental mouse counterpart, including binding kinetics to CD34 and blockage of tube formation of HUVECs.

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