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

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Abstract

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.

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Acknowledgments

The authors acknowledge and thank the American Association of Pharmaceutical Scientists (AAPS) for supporting the short course and recognize the scientists dedicated to defining the ADC development path. The authors would like to specifically acknowledge Dr. Charles Foerder for serving as a presenter and panelist at the AAPS annual meeting.

Author’s Contribution

M.B.H. and K.T. prepared the manuscript for publication. M.B.H., K.T., M.C.T., and N.F.S. wrote and reviewed the manuscript. K.T. organized and moderated the AAPS session. M.B.H., M.C.T., and N.F.S. presented during the short course and served as panelists for the panel session.

Conflict of Interest

K.T. is employed by Novartis Pharmaceuticals and declares no competing financial interests. M.B.H. is employed at Amgen and declares no competing financial interests. M.C.T. is employed by Genentech and declares no competing financial interests. N.F.S. is the CEO of ProImmune and declares no competing financial interests.

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Authors and Affiliations

  1. Department of Clinical Immunology, Amgen Inc., One Amgen Center Dr., 30E-3-B, Thousand Oaks, California, 91320, USA

    M. Benjamin Hock

  2. Oncology Clinical Pharmacology, Novartis Pharmaceuticals, One Health Plaza, BLDG 337, East Hanover, New Jersey, 07936, USA

    Karen E. Thudium

  3. BioAnalytical Sciences, Genentech, South San Francisco, California, USA

    Montserrat Carrasco-Triguero

  4. ProImmune Ltd., Oxford, UK

    Nikolai F. Schwabe

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  1. M. Benjamin Hock
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  2. Karen E. Thudium
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  4. Nikolai F. Schwabe
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Correspondence to M. Benjamin Hock or Karen E. Thudium.

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Hock, M.B., Thudium, K.E., Carrasco-Triguero, M. et al. Immunogenicity of Antibody Drug Conjugates: Bioanalytical Methods and Monitoring Strategy for a Novel Therapeutic Modality. AAPS J 17, 35–43 (2015). https://doi.org/10.1208/s12248-014-9684-6

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