Premium
Engineering of Monovalent, Multivalent and Bispecific Antibodies for New Therapeutic Applications
Author(s) -
Lugovskoy Alexey Alexandrovich,
Farrington Graham,
Miller Brian,
Glaser Scott
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.415.2
Subject(s) - bispecific antibody , thermostability , antibody , bivalent (engine) , chemistry , rational design , epitope , small molecule , protein engineering , antigen , computational biology , combinatorial chemistry , biophysics , biochemistry , nanotechnology , immunology , biology , monoclonal antibody , materials science , enzyme , organic chemistry , metal
Engineered bispecific and tetravalent IgG‐like antibodies that engage multiple target epitopes represent promising new classes of therapeutic agents. To address their intrinsic low stability and high aggregation propensity, we applied rational design to increase the thermostability of single chain Fv fragments without compromising their affinity towards antigen. Incorporation of these stabilized modules into full‐length therapeutic bispecific and tetravalent molecules led to molecules with markedly improved properties. We additionally describe the development and characterization of new monovalent and heteromeric antibody platforms that allow us to interrogate the classes of targets, such as receptor tyrosine kinases and cytokines, which may be difficult to inhibit by bivalent antibodies.