期刊
GROWTH FACTORS
卷 32, 期 6, 页码 223-235出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/08977194.2014.984808
关键词
ADCC; EphA3; Humaneered; leukemia; non-fucosylated
EphA3is expressed in solid tumors and leukemias and is an attractive target for the therapy. We have generated a panel of Humaneered (R) antibodies to the ligand-binding domain using a Fab epitope-focused library that has the same specificity as monoclonal antibody mIIIA4. A high-affinity antibody was selected that competes with the mIIIA4 antibody for binding to EphA3 and has an improved affinity of similar to 1 nM. In order to generate an antibody with potent cell-killing activity the variable regions were assembled with human IgG1k constant regions and expressed in a Chinese hamster ovary (CHO) cell line deficient in fucosyl transferase. Non-fucosylated antibodies have been reported to have enhanced binding affinity for the IgG receptor CD16a (Fc gamma RIIIa). The affinity of the antibody for recombinant CD16a was enhanced approximately 10-fold. This resulted in enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity against EphA3-expressing leukemic cells, providing a potent antibody for the evaluation as a therapeutic agent.
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