Abstract:
:A mono-specific antibody may recruit a second antigen binding specificity, thus converting to a dual-specific Two-in-One antibody through mutation at the light chain complementarity-determining regions (CDRs). It is, however, unknown whether mutation at the heavy chain CDRs may evolve such dual specificity. Herein, we examined the CDRs of a humanized interleukin 4 (IL4) antibody using alanine scanning and structural modeling, designed libraries of mutants in regions that tolerate mutation, and isolated dual specific antibodies harboring mutation at the heavy chain CDRs only. We then affinity improved an IL4/IL5 dual specific antibody to variants with dissociation constants in the low nanomolar range for both antigens. The results demonstrate the full capacity of antibodies to evolve dual binding specificity.
journal_name
MAbsjournal_title
mAbsauthors
Lee CV,Koenig P,Fuh Gdoi
10.4161/mabs.28483subject
Has Abstractpub_date
2014-05-01 00:00:00pages
622-7issue
3eissn
1942-0862issn
1942-0870pii
28483journal_volume
6pub_type
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