Affinity maturation and characterization of the ofatumumab monoclonal antibody.
Animals
Antibodies, Monoclonal, Humanized
/ genetics
Antibody Affinity
/ immunology
Antigens, CD20
/ chemistry
B-Lymphocytes
/ immunology
CHO Cells
Cricetulus
Drug Design
Enzyme-Linked Immunosorbent Assay
Genetic Vectors
/ genetics
Immunoglobulin Heavy Chains
/ genetics
Immunoglobulin Light Chains
/ genetics
Kinetics
Leukemia, Lymphocytic, Chronic, B-Cell
/ drug therapy
Mutant Proteins
Mutation
Plasmids
/ genetics
Surface Plasmon Resonance
Transfection
CD20
affinity binding
chronic lymphocytic leukemia
monoclonal antibodies
ofatumumab
Journal
Journal of cellular biochemistry
ISSN: 1097-4644
Titre abrégé: J Cell Biochem
Pays: United States
ID NLM: 8205768
Informations de publication
Date de publication:
01 2019
01 2019
Historique:
received:
26
05
2018
accepted:
25
07
2018
pubmed:
31
8
2018
medline:
26
2
2020
entrez:
31
8
2018
Statut:
ppublish
Résumé
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.
Substances chimiques
Antibodies, Monoclonal, Humanized
0
Antigens, CD20
0
Immunoglobulin Heavy Chains
0
Immunoglobulin Light Chains
0
Mutant Proteins
0
ofatumumab
M95KG522R0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
940-950Informations de copyright
© 2018 Wiley Periodicals, Inc.