Premium
Affinity maturation and characterization of the ofatumumab monoclonal antibody
Author(s) -
Payandeh Zahra,
Rajabibazl Masoumeh,
Mortazavi Yousef,
Rahimpour Azam,
Taromchi Amir Hossein,
Dastmalchi Siavoush
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27457
Subject(s) - ofatumumab , monoclonal antibody , antibody , chinese hamster ovary cell , polyclonal antibodies , chronic lymphocytic leukemia , cd20 , microbiology and biotechnology , chemistry , antigen , cancer research , computational biology , biology , biochemistry , leukemia , immunology , receptor
CD20 molecule, a phosphoprotein with 297 amino acids and four transmembrane domains, is a member of MS4A protein family. Anti‐CD20 antibodies such as ofatumumab, which have been developed for cancer treatment and has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. Rational engineering methods can be applied with reasonable success to improve functional characteristics of antibodies. Considering the importance of this issue, we have used in silico modeling approach for the improvement of ofatumumab monoclonal antibody. Four mutated variants of ofatumumab were developed and expressed in Chinese hamster ovary (CHO) cells along with the unmodified antibody. Analysis of affinity of the purified antibodies with CD20 showed significant improvement in antigen‐binding characteristics of one of the variants compared with the control antibody. This study represents the first step toward development of the second generation ofatumumab antibody with improved affinity.