In:
Advanced Therapeutics, Wiley, Vol. 1, No. 3 ( 2018-07)
Abstract:
The vast information available on hierarchically structured proteins enables the creation of novel proteins with customized functions through the assembly of independent functional component modules. Here, a compact T cell–activating antibody is constructed from the antigen‐binding modules of variable domains. Genetic fusion of a single variable domain of the heavy chain of a heavy chain llama antibody (VHH) to the human single‐chain variable region of an antigen‐binding fragment (scFv), which is designed to be dimerized, yields a compact bispecific and bivalent antibody (BiBian) with a seahorse‐shaped structure. BiBian recognizes epidermal growth factor receptor (EGFR) on cancer cells and CD3 receptors on T cells; the two VHHs and dimerized scFv are structurally independent and positioned such that they are easily accessible to each target. BiBian adhered strongly to both cancer cells and T cells, promoted T cell activation (due to the bivalent CD3 modules), and induced dramatic cytotoxicity against tumor spheroids in vitro and in vivo. This compact structure is proposed as a fundamental format for homogeneous, highly cytotoxic, bacterially expressed antibodies.
Type of Medium:
Online Resource
ISSN:
2366-3987
,
2366-3987
DOI:
10.1002/adtp.201700031
Language:
English
Publisher:
Wiley
Publication Date:
2018
detail.hit.zdb_id:
2920320-X
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