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Considerations in Establishing Affinity Design Goals for Development of Antibody-Based Therapeutics

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Development of Antibody-Based Therapeutics

Abstract

Establishing design goals with respect to antibody affinity is a critical consideration that should be incorporated into development strategies from the earliest stages of the discovery process for antibody-based therapeutics. Selection of the adequate affinity for a functional antibody should allow achievement of the maximum therapeutic benefit at a dose associated with a manageable cost of goods and the intended route of administration. Application of theoretical pharmacokinetic (PK) and pharmacodynamic (PD) modeling with incorporation of relevant parameters with respect to antibody PK properties and biodistribution, antigen turnover rate, and antigen concentrations under physiological and pathological conditions can facilitate determination of the optimum affinity required. This chapter will review the critical considerations necessary for the design of optimum affinity goals for antibody-based therapeutics.

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References

  • Bornstein GG, Queva C, Tabrizi M, Abbema AV, Chavez C, Wang P et al (2009) Development of a new fully human anti-CD20 monoclonal antibody for the treatment of B-cell malignancies. Invest New Drugs. doi:10.1007/s10637-009-9291-z

    PubMed  Google Scholar 

  • Desjarlais JR, Lazar GA, Zhukovsky EA, Chu SY (2007) Optimizing engagement of the immune system by anti-tumor antibodies: an engineer’s perspective. Drug Discov Today 12(21–22):898–910

    Article  PubMed  CAS  Google Scholar 

  • Graff CP, Wittrup KD (2003) Theoretical analysis of antibody targeting of tumor spheroids: importance of dosage for penetration, and affinity for retention. Cancer Res 63(6):1288–1296

    PubMed  CAS  Google Scholar 

  • Moore GL, Chen H, Karki S, Lazar GA (2010) Engineered Fc variant antibodies with enhanced ability to recruit complement and mediate effector functions. MAbs 2(2):181–189

    Google Scholar 

  • Roskos L, Klakamp SL, Liang M, Arends R, Green L (2007) Molecular engineering II: antibody affinity. In: Dubel S (ed) Handbook of therapeutic antibodes. Wiley, pp 149–169

    Google Scholar 

  • Tabrizi MA, Bornstein GG, Klakamp SL, Drake A, Knight R, Roskos L (2009a) Translational strategies for development of monoclonal antibodies from discovery to the clinic. Drug Discov Today 14(5–6):298–305

    Article  PubMed  CAS  Google Scholar 

  • Tabrizi M, Bornstein GG, Suria H (2009b) Biodistribution mechanisms of therapeutic monoclonal antibodies in health and disease. AAPS J 12:33–43. doi:10.1208/s12248-009-9157-5

    Article  PubMed  Google Scholar 

  • Tabrizi M, Funelas C, Suria H (2010) Application of quantitative pharmacology in development of therapeutic monoclonal antibodies. AAPS J 12(4):592–601. doi: 10.1208/s12248-010-9220-2

    Google Scholar 

  • Thurber GM, Zajic SC, Wittrup KD (2007) Theoretic criteria for antibody penetration into solid tumors and micrometastases. J Nucl Med 48(6):995–999

    Article  PubMed  CAS  Google Scholar 

  • Thurber GM, Schmidt MM, Wittrup KD (2008a) Factors determining antibody distribution in tumors. Trends Pharmacol Sci 29(2):57–61

    PubMed  CAS  Google Scholar 

  • Thurber GM, Schmidt MM, Wittrup KD (2008b) Antibody tumor penetration: transport opposed by systemic and antigen-mediated clearance. Adv Drug Deliv Rev 60(12):1421–1434

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Mohammad Tabrizi .

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© 2012 Springer Science+Business Media New York

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Tabrizi, M. (2012). Considerations in Establishing Affinity Design Goals for Development of Antibody-Based Therapeutics. In: Tabrizi, M., Bornstein, G., Klakamp, S. (eds) Development of Antibody-Based Therapeutics. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-5955-3_6

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  • DOI: https://doi.org/10.1007/978-1-4419-5955-3_6

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  • Publisher Name: Springer, New York, NY

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  • Online ISBN: 978-1-4419-5955-3

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