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2018 ; 10
(2
): 256-268
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Productive common light chain libraries yield diverse panels of high affinity
bispecific antibodies
#MMPMID29227213
Van Blarcom T
; Lindquist K
; Melton Z
; Cheung WL
; Wagstrom C
; McDonough D
; Valle Oseguera C
; Ding S
; Rossi A
; Potluri S
; Sundar P
; Pitts S
; Sirota M
; Galindo Casas M
; Yan Y
; Jones J
; Roe-Zurz Z
; Srivatsa Srinivasan S
; Zhai W
; Pons J
; Rajpal A
; Chaparro-Riggers J
MAbs
2018[Feb]; 10
(2
): 256-268
PMID29227213
show ga
The commercial success of bispecific antibodies generally has been hindered by
the complexities associated with generating appropriate molecules for both
research scale and large scale manufacturing purposes. Bispecific IgG (BsIgG)
based on two antibodies that use an identical common light chain can be combined
with a minimal set of Fc mutations to drive heavy chain heterodimerization in
order to address these challenges. However, the facile generation of common light
chain antibodies with properties similar to traditional monoclonal antibodies has
not been demonstrated and they have only been used sparingly. Here, we describe
the design of a synthetic human antibody library based on common light chains to
generate antibodies with biochemical and biophysical properties that are
indistinguishable to traditional therapeutic monoclonal antibodies. We used this
library to generate diverse panels of well-behaved, high affinity antibodies
toward a variety of epitopes across multiple antigens, including mouse 4-1BB, a
therapeutically important T cell costimulatory receptor. Over 200 BsIgG toward
4-1BB were generated using an automated purification method we developed that
enables milligram-scale production of BsIgG. This approach allowed us to identify
antibodies with a wide range of agonistic activity that are being used to further
investigate the therapeutic potential of antibodies targeting one or more
epitopes of 4-1BB.