AJICAP™: Development of a Site-Specific Chemical Conjugation Technology for Antibody-Drug Conjugates

DOI
  • Yamada Kei
    Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc.
  • Matsuda Yutaka
    Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc. Ajinomoto Bio-Pharma Services
  • Seki Takuya
    Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc.
  • Mendelsohn Brian A.
    Ajinomoto Bio-Pharma Services
  • Okuzumi Tatsuya
    Research Institute for Bioscience Products and Fine Chemicals, Ajinomoto Co., Inc.

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Other Title
  • AJICAP™：位置特異的ADCの次世代化学合成法の開発

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Description

<p>Antibody-drug conjugates (ADCs) have become a major class of cancer biopharmaceuticals and traditional ADCs have a stochastic distribution of cytotoxic drugs linked across several different sites of the antibody. The heterogeneous nature of resulting stochastic ADCs can cause diminished efficacy and increased toxicity, thus limiting the corresponding therapeutic index. To improve on traditional ADC technology, we developed and report here a novel chemical conjugation platform termed “AJICAP™” for the site-specific modification of native antibodies through the use of a class of IgG Fc-affinity reagents. Site-specific installation of thiol functional groups to well-defined lysine residues in IgGs followed by conjugation to these newly installed thiols with cytotoxic payloads was efficiently conducted to generate AJICAP™-ADCs. Several results described that AJICAP™-ADCs expand the therapeutic window compare to random conjugated ADCs. AJICAP™ technology is a powerful platform to enable next-generation ADCs through the reduction of heterogeneity and enhanced of therapeutic index.</p>

Journal

  • MEDCHEM NEWS

    MEDCHEM NEWS 30 (3), 137-144, 2020-08-01

    The Pharmaceutical Society of Japan

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