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Literature DB >> 20081867

Enhanced antibody half-life improves in vivo activity.

Jonathan Zalevsky¹, Aaron K Chamberlain, Holly M Horton, Sher Karki, Irene W L Leung, Thomas J Sproule, Greg A Lazar, Derry C Roopenian, John R Desjarlais.

Abstract

Improved affinity for the neonatal Fc receptor (FcRn) is known to extend antibody half-life in vivo. However, this has never been linked with enhanced therapeutic efficacy. We tested whether antibodies with half-lives extended up to fivefold in human (h)FcRn transgenic mice and threefold in cynomolgus monkeys retain efficacy at longer dosing intervals. We observed that prolonged exposure due to FcRn-mediated enhancement of half-life improved antitumor activity of Fc-engineered antibodies in an hFcRn/Rag1(-/-) mouse model. This bridges the demand for dosing convenience with the clinical necessity of maintaining efficacy.

Entities: CellLine Chemical Disease Gene Mutation Species

Mesh：

Substances：
Antibodies, Monoclonal

Year: 2010 PMID： 20081867 PMCID： PMC2855492 DOI： 10.1038/nbt.1601

Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908

14 in total

1. Engineered human IgG antibodies with longer serum half-lives in primates.

Authors: Paul R Hinton; Mary G Johlfs; Joanna M Xiong; Kelly Hanestad; Kelly C Ong; Chuck Bullock; Stephen Keller; Meina Tao Tang; J Yun Tso; Max Vásquez; Naoya Tsurushita
Journal: J Biol Chem Date: 2003-12-29 Impact factor: 5.157

2. Properties of human IgG1s engineered for enhanced binding to the neonatal Fc receptor (FcRn).

Authors: William F Dall'Acqua; Peter A Kiener; Herren Wu
Journal: J Biol Chem Date: 2006-06-21 Impact factor: 5.157

3. An engineered human IgG1 antibody with longer serum half-life.

Authors: Paul R Hinton; Joanna M Xiong; Mary G Johlfs; Meina Tao Tang; Stephen Keller; Naoya Tsurushita
Journal: J Immunol Date: 2006-01-01 Impact factor: 5.422

4. Preclinical pharmacokinetics, interspecies scaling, and tissue distribution of a humanized monoclonal antibody against vascular endothelial growth factor.

Authors: Y S Lin; C Nguyen; J L Mendoza; E Escandon; D Fei; Y G Meng; N B Modi
Journal: J Pharmacol Exp Ther Date: 1999-01 Impact factor: 4.030

5. Humanization of an anti-vascular endothelial growth factor monoclonal antibody for the therapy of solid tumors and other disorders.

Authors: L G Presta; H Chen; S J O'Connor; V Chisholm; Y G Meng; L Krummen; M Winkler; N Ferrara
Journal: Cancer Res Date: 1997-10-15 Impact factor: 12.701

6. Effect of target dynamics on pharmacokinetics of a novel therapeutic antibody against the epidermal growth factor receptor: implications for the mechanisms of action.

Authors: Jeroen J Lammerts van Bueren; Wim K Bleeker; Henrik O Bøgh; Mischa Houtkamp; Janine Schuurman; Jan G J van de Winkel; Paul W H I Parren
Journal: Cancer Res Date: 2006-08-01 Impact factor: 12.701

7. Antibody-induced epidermal growth factor receptor dimerization mediates inhibition of autocrine proliferation of A431 squamous carcinoma cells.

Authors: Z Fan; Y Lu; X Wu; J Mendelsohn
Journal: J Biol Chem Date: 1994-11-04 Impact factor: 5.157

8. Enhanced half-life of genetically engineered human IgG1 antibodies in a humanized FcRn mouse model: potential application in humorally mediated autoimmune disease.

Authors: Stefka B Petkova; Shreeram Akilesh; Thomas J Sproule; Gregory J Christianson; Hana Al Khabbaz; Aaron C Brown; Leonard G Presta; Y Gloria Meng; Derry C Roopenian
Journal: Int Immunol Date: 2006-10-31 Impact factor: 4.823

9. Therapeutic potential of chimeric and murine anti-(epidermal growth factor receptor) antibodies in a metastasis model for human melanoma.

Authors: M Naramura; S D Gillies; J Mendelsohn; R A Reisfeld; B M Mueller
Journal: Cancer Immunol Immunother Date: 1993-10 Impact factor: 6.968

10. Engineering human IgG1 affinity to human neonatal Fc receptor: impact of affinity improvement on pharmacokinetics in primates.

Authors: Yik Andy Yeung; Maya K Leabman; Jonathan S Marvin; Julia Qiu; Camellia W Adams; Samantha Lien; Melissa A Starovasnik; Henry B Lowman
Journal: J Immunol Date: 2009-06-15 Impact factor: 5.422

218 in total

1. Maternal antibody persistence: a neglected life-history trait with implications from albatross conservation to comparative immunology.

Authors: R Garnier; R Ramos; V Staszewski; T Militão; E Lobato; J González-Solís; T Boulinier
Journal: Proc Biol Sci Date: 2011-12-21 Impact factor: 5.349

2. A novel bispecific antibody format enables simultaneous bivalent and monovalent co-engagement of distinct target antigens.

Authors: Gregory L Moore; Cristina Bautista; Erik Pong; Duc-Hanh T Nguyen; Jonathan Jacinto; Araz Eivazi; Umesh S Muchhal; Sher Karki; Seung Y Chu; Greg A Lazar
Journal: MAbs Date: 2011-11-01 Impact factor: 5.857

3. 7th annual European Antibody Congress 2011: November 29-December 1, 2011, Geneva, Switzerland.

Authors: Alexey A Lugovskoy; Janice M Reichert; Alain Beck
Journal: MAbs Date: 2012-03-01 Impact factor: 5.857

Review 4. Research and development of next generation of antibody-based therapeutics.

Authors: Jing Li; Zhenping Zhu
Journal: Acta Pharmacol Sin Date: 2010-08-09 Impact factor: 6.150

5. Scale-up of a physiologically-based pharmacokinetic model to predict the disposition of monoclonal antibodies in monkeys.

Authors: Patrick M Glassman; Yang Chen; Joseph P Balthasar
Journal: J Pharmacokinet Pharmacodyn Date: 2015-09-12 Impact factor: 2.745

10. A Minimal Physiologically Based Pharmacokinetic Model with a Nested Endosome Compartment for Novel Engineered Antibodies.

Authors: Dongfen Yuan; Frederik Rode; Yanguang Cao
Journal: AAPS J Date: 2018-03-14 Impact factor: 4.009