Bioassay Development for Bispecific Antibodies-Challenges and Opportunities

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Jun 2

PMID 34069573

Citations 11

Authors

Ames C Register

Somayeh S Tarighat

Ho Young Lee

Affiliations

Soon will be listed here.

Abstract

Antibody therapeutics are expanding with promising clinical outcomes, and diverse formats of antibodies are further developed and available for patients of the most challenging disease areas. Bispecific antibodies (BsAbs) have several significant advantages over monospecific antibodies by engaging two antigen targets. Due to the complicated mechanism of action, diverse structural variations, and dual-target binding, developing bioassays and other types of assays to characterize BsAbs is challenging. Developing bioassays for BsAbs requires a good understanding of the mechanism of action of the molecule, principles and applications of different bioanalytical methods, and phase-appropriate considerations per regulatory guidelines. Here, we review recent advances and case studies to provide strategies and insights for bioassay development for different types of bispecific molecules.

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References

Agez M, Mandon E, Iwema T, Gianotti R, Limani F, Herter S . Biochemical and biophysical characterization of purified native CD20 alone and in complex with rituximab and obinutuzumab. Sci Rep. 2019; 9(1):13675. PMC: 6757138. DOI: 10.1038/s41598-019-50031-4. View

Veri M, Burke S, Huang L, Li H, Gorlatov S, Tuaillon N . Therapeutic control of B cell activation via recruitment of Fcgamma receptor IIb (CD32B) inhibitory function with a novel bispecific antibody scaffold. Arthritis Rheum. 2010; 62(7):1933-43. DOI: 10.1002/art.27477. View

Lum L, Davol P, Lee R . The new face of bispecific antibodies: targeting cancer and much more. Exp Hematol. 2006; 34(1):1-6. DOI: 10.1016/j.exphem.2005.07.013. View

Godar M, Deswarte K, Vergote K, Saunders M, de Haard H, Hammad H . A bispecific antibody strategy to target multiple type 2 cytokines in asthma. J Allergy Clin Immunol. 2018; 142(4):1185-1193.e4. PMC: 7610797. DOI: 10.1016/j.jaci.2018.06.002. View

Nguyen H, Park J, Kang S, Kim M . Surface plasmon resonance: a versatile technique for biosensor applications. Sensors (Basel). 2015; 15(5):10481-510. PMC: 4481982. DOI: 10.3390/s150510481. View

Couch J, Yu Y, Zhang Y, Tarrant J, Fuji R, Meilandt W . Addressing safety liabilities of TfR bispecific antibodies that cross the blood-brain barrier. Sci Transl Med. 2013; 5(183):183ra57, 1-12. DOI: 10.1126/scitranslmed.3005338. View

Sun L, Ellerman D, Mathieu M, Hristopoulos M, Chen X, Li Y . Anti-CD20/CD3 T cell-dependent bispecific antibody for the treatment of B cell malignancies. Sci Transl Med. 2015; 7(287):287ra70. DOI: 10.1126/scitranslmed.aaa4802. View

Stracke J, Emrich T, Rueger P, Schlothauer T, Kling L, Knaupp A . A novel approach to investigate the effect of methionine oxidation on pharmacokinetic properties of therapeutic antibodies. MAbs. 2014; 6(5):1229-42. PMC: 4622569. DOI: 10.4161/mabs.29601. View

Watanabe M, Wallace P, Keler T, Deo Y, Akewanlop C, Hayes D . Antibody dependent cellular phagocytosis (ADCP) and antibody dependent cellular cytotoxicity (ADCC) of breast cancer cells mediated by bispecific antibody, MDX-210. Breast Cancer Res Treat. 1999; 53(3):199-207. DOI: 10.1023/a:1006145507567. View

10.

Wang Q, Chen Y, Park J, Liu X, Hu Y, Wang T . Design and Production of Bispecific Antibodies. Antibodies (Basel). 2019; 8(3). PMC: 6783844. DOI: 10.3390/antib8030043. View

11.

Yu S, Liu Q, Han X, Qin S, Zhao W, Li A . Development and clinical application of anti-HER2 monoclonal and bispecific antibodies for cancer treatment. Exp Hematol Oncol. 2017; 6:31. PMC: 5704598. DOI: 10.1186/s40164-017-0091-4. View

12.

Niewoehner J, Bohrmann B, Collin L, Urich E, Sade H, Maier P . Increased brain penetration and potency of a therapeutic antibody using a monovalent molecular shuttle. Neuron. 2014; 81(1):49-60. DOI: 10.1016/j.neuron.2013.10.061. View

13.

Koopmans I, Hendriks M, van Ginkel R, Samplonius D, Bremer E, Helfrich W . Bispecific Antibody Approach for Improved Melanoma-Selective PD-L1 Immune Checkpoint Blockade. J Invest Dermatol. 2019; 139(11):2343-2351.e3. DOI: 10.1016/j.jid.2019.01.038. View

14.

Wu C, Ying H, Grinnell C, Bryant S, Miller R, Clabbers A . Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin. Nat Biotechnol. 2007; 25(11):1290-7. DOI: 10.1038/nbt1345. View

15.

Tourdot S, Hickling T . Nonclinical immunogenicity risk assessment of therapeutic proteins. Bioanalysis. 2019; 11(17):1631-1643. DOI: 10.4155/bio-2018-0246. View

16.

Kontermann R . Strategies to extend plasma half-lives of recombinant antibodies. BioDrugs. 2009; 23(2):93-109. DOI: 10.2165/00063030-200923020-00003. View

17.

Spiess C, Zhai Q, Carter P . Alternative molecular formats and therapeutic applications for bispecific antibodies. Mol Immunol. 2015; 67(2 Pt A):95-106. DOI: 10.1016/j.molimm.2015.01.003. View

18.

Piscopo N, Mueller K, Das A, Hematti P, Murphy W, Palecek S . Bioengineering Solutions for Manufacturing Challenges in CAR T Cells. Biotechnol J. 2017; 13(2). PMC: 5796845. DOI: 10.1002/biot.201700095. View

19.

Meschendoerfer W, Gassner C, Lipsmeier F, Regula J, Moelleken J . SPR-based assays enable the full functional analysis of bispecific molecules. J Pharm Biomed Anal. 2016; 132:141-147. DOI: 10.1016/j.jpba.2016.09.028. View

20.

Pahl J, Koch J, Gotz J, Arnold A, Reusch U, Gantke T . CD16A Activation of NK Cells Promotes NK Cell Proliferation and Memory-Like Cytotoxicity against Cancer Cells. Cancer Immunol Res. 2018; 6(5):517-527. DOI: 10.1158/2326-6066.CIR-17-0550. View