Engineering the variable region of therapeutic IgG antibodies
- PMID: 21406966
- PMCID: PMC3149705
- DOI: 10.4161/mabs.3.3.15234
Engineering the variable region of therapeutic IgG antibodies
Abstract
Since the first generation of humanized IgG1 antibodies reached the market in the late 1990s, IgG antibody molecules have been extensively engineered. The success of antibody therapeutics has introduced severe competition in developing novel therapeutic monoclonal antibodies, especially for promising or clinically validated targets. Such competition has led researchers to generate so-called second or third generation antibodies with clinical differentiation utilizing various engineering and optimization technologies. Parent IgG antibodies can be engineered to have improved antigen binding properties, effector functions, pharmacokinetics, pharmaceutical properties and safety issues. Although the primary role of the antibody variable region is to bind to the antigen, it is also the main source of antibody diversity and its sequence affects various properties important for developing antibody therapeutics. Here we review recent research activity in variable region engineering to generate superior antibody therapeutics.
Similar articles
-
Humanization and Simultaneous Optimization of Monoclonal Antibody.Methods Mol Biol. 2019;1904:213-230. doi: 10.1007/978-1-4939-8958-4_9. Methods Mol Biol. 2019. PMID: 30539472
-
Fc Engineering of Human IgG1 for Altered Binding to the Neonatal Fc Receptor Affects Fc Effector Functions.J Immunol. 2015 Jun 1;194(11):5497-508. doi: 10.4049/jimmunol.1401218. Epub 2015 Apr 22. J Immunol. 2015. PMID: 25904551 Free PMC article.
-
[Transgenesis and humanization of murine antibodies].Med Sci (Paris). 2009 Dec;25(12):1149-54. doi: 10.1051/medsci/200925121149. Med Sci (Paris). 2009. PMID: 20035696 Review. French.
-
Structural correlates of an anticarcinoma antibody: identification of specificity-determining residues (SDRs) and development of a minimally immunogenic antibody variant by retention of SDRs only.J Immunol. 2000 Feb 1;164(3):1432-41. doi: 10.4049/jimmunol.164.3.1432. J Immunol. 2000. PMID: 10640759
-
Pharmacokinetics and biodistribution of genetically-engineered antibodies.Q J Nucl Med. 1998 Dec;42(4):225-41. Q J Nucl Med. 1998. PMID: 9973838 Review.
Cited by
-
Balancing the Affinity and Tumor Cell Binding of a Two-in-One Antibody Simultaneously Targeting EGFR and PD-L1.Antibodies (Basel). 2024 May 2;13(2):36. doi: 10.3390/antib13020036. Antibodies (Basel). 2024. PMID: 38804304 Free PMC article.
-
Efficient production of bispecific antibody by FAST-IgTM and its application to NXT007 for the treatment of hemophilia A.MAbs. 2023 Jan-Dec;15(1):2222441. doi: 10.1080/19420862.2023.2222441. MAbs. 2023. PMID: 37339067 Free PMC article.
-
Complement Activation by an Anti-Dengue/Zika Antibody with Impaired Fcγ Receptor Binding Provides Strong Efficacy and Abrogates Risk of Antibody-Dependent Enhancement.Antibodies (Basel). 2023 May 15;12(2):36. doi: 10.3390/antib12020036. Antibodies (Basel). 2023. PMID: 37218902 Free PMC article.
-
Studying the characteristics of nanobody CDR regions based on sequence analysis in combination with 3D structures.J Genet Eng Biotechnol. 2022 Nov 21;20(1):157. doi: 10.1186/s43141-022-00439-9. J Genet Eng Biotechnol. 2022. PMID: 36417012 Free PMC article.
-
Pharmacokinetic Developability and Disposition Profiles of Bispecific Antibodies: A Case Study with Two Molecules.Antibodies (Basel). 2021 Dec 28;11(1):2. doi: 10.3390/antib11010002. Antibodies (Basel). 2021. PMID: 35076469 Free PMC article.
References
-
- Chan AC, Carter PJ. Therapeutic antibodies for autoimmunity and inflammation. Nature Rev Immunol. 2010;10:301–316. - PubMed
-
- Strohl WR. Therapeutic monoclonal antibodies-past, present and future. In: An Z, editor. Therapeutic Monoclonal Antibodies: From Bench to Clinic. New York: John Wiley & Sons; 2009. pp. 4–50.
-
- Strohl WR. Optimization of Fc-mediated effector functions of monoclonal antibodies. Curr Opin Biotechnol. 2009;20:685–691. - PubMed
-
- Batista FD, Neuberger MS. Affinity dependence of the B cell response to antigen: a threshold, a ceiling and the importance of off-rate. Immunity. 1998;8:751–759. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources