A two-in-one antibody engineered from a humanized interleukin 4 antibody through mutation in heavy chain complementarity-determining regions.

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

MAbs

journal_title

mAbs

authors

Lee CV,Koenig P,Fuh G

doi

10.4161/mabs.28483

subject

Has Abstract

pub_date

2014-05-01 00:00:00

pages

622-7

issue

3

eissn

1942-0862

issn

1942-0870

pii

28483

journal_volume

6

pub_type

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