Immunogenicity of Antibody Drug Conjugates: Bioanalytical Methods and Monitoring Strategy for a Novel Therapeutic Modality

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• 作者：M. Benjamin Hock (1)
  Karen E. Thudium (2)
  Montserrat Carrasco-Triguero (3)
  Nikolai F. Schwabe (4)
  
  1. Department of Clinical Immunology ; Amgen Inc. ; One Amgen Center Dr. ; 30E-3-B ; Thousand Oaks ; California ; 91320 ; USA
  2. Oncology Clinical Pharmacology ; Novartis Pharmaceuticals ; One Health Plaza ; BLDG 337 ; East Hanover ; New Jersey ; 07936 ; USA
  3. BioAnalytical Sciences ; Genentech ; South San Francisco ; California ; USA
  4. ProImmune Ltd. ; Oxford ; UK
  
• 关键词：antibody ; drug conjugate (ADC) ; antidrug antibodies (ADA) ; bioanalytical ; immunogenicity ; oncology
• 刊名：The AAPS Journal
• 出版年：2015
• 出版时间：January 2015
• 年：2015
• 卷：17
• 期：1
• 页码：35-43
• 全文大小：256 KB
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• 刊物主题：Pharmacology/Toxicology; Biochemistry, general; Biotechnology; Pharmacy;
• 出版者：Springer US
• ISSN：1550-7416

文摘

Immunogenicity (the development of an adaptive immune response reactive with a therapeutic) is a well-described but unwanted facet of biotherapeutic development. There are commonly applied procedures for immunogenicity risk assessment, testing strategies, and bioanalysis. With some modifications, these can be applied to new biotherapeutic modalities. For novel therapies such as antibody-drug conjugates (ADCs), the unique structural components may contribute additional complexities to both immunologic responses and bioanalytical methods. US product inserts (USPIs) for two commercially available ADCs detail the incidence of immunogenicity; however, the body of literature on immunogenicity of ADCs is limited. We recently participated in a conference session on this topic (Annual meeting of the American Association of Pharmaceutical Scientists, held November 2013 in San Antonio, TX, USA. The meeting featured the Symposium: Immunogenicity Assessment for Novel Antibody Drug Conjugates, Nonclinical to Clinical) which prompted an effort to share our perspectives on how immunogenicity risk assessment, testing strategies, and bioanalytical methods can be adapted to reflect the complexity of ADC therapeutics.