期刊
MABS
卷 12, 期 1, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/19420862.2020.1812210
关键词
Antibody engineering; bispecific antibody; camelid; IgG-like; nanobody; single-domain antibody; trispecific antibody; VHH
Here, we report the characterization of a VHH-derived IgG-like bi- and trispecific antibody platform that essentially relies on the replacement of the VH and VL regions of a conventional antibody by two independently functioning VHH domains. Consequently, a VHH is engrafted onto constant region CH1 while the other VHH-based paratope is engrafted on the constant region of the light chain, C kappa or C lambda, resulting in a tetravalent bispecific IgG-like molecule. Combined with a heavy chain heterodimerization technique, this platform allows facile engineering of bi- and trispecific antibodies with flexible valencies. We demonstrate the general applicability of this generic platform approach and elaborate on the limitations of specific formats.
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