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High-Throughput Platform to Identify Antibody Conjugation Sites from Antibody-Drug Conjugate Libraries.
Yamazoe, Sayumi; Hogan, Jason M; West, Sean M; Deng, Xiaodi A; Kotapati, Srikanth; Shao, Xiang; Holder, Patrick; Lamba, Vandana; Huber, Mary; Qiang, Cong; Gangwar, Sanjeev; Rao, Chetana; Dollinger, Gavin; Rajpal, Arvind; Strop, Pavel.
Afiliação
  • Yamazoe S; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Hogan JM; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • West SM; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Deng XA; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Kotapati S; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Shao X; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Holder P; Protein Chemistry, Genentech Research and Early Development, 501 DNA Way, South San Francisco, California 94080, United States.
  • Lamba V; Centers for Therapeutic Innovation, Pfizer Inc., 1700 Owens Street, San Francisco, California 94158, United States.
  • Huber M; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Qiang C; Discovery Chemistry Oncology, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Gangwar S; Discovery Chemistry Oncology, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Rao C; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Dollinger G; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Rajpal A; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
  • Strop P; Discovery Biotherapeutics, Bristol-Myers Squibb, 700 Bay Road, Redwood City, California 94063, United States.
Bioconjug Chem ; 31(4): 1199-1208, 2020 04 15.
Article em En | MEDLINE | ID: mdl-32178516
ABSTRACT
Antibody-drug conjugates (ADCs) are a therapeutic modality that traditionally enable the targeted delivery of highly potent cytotoxic agents to specific cells such as tumor cells. More recently, antibodies have been used to deliver molecules such as antibiotics, antigens, and adjuvants to bacteria or specific immune cell subsets. Site-directed mutagenesis of proteins permits more precise control over the site and stoichiometry of their conjugation, giving rise to homogeneous chemically defined ADCs. Identification of favorable sites for conjugation in antibodies is essential as reaction efficiency and product stability are influenced by the tertiary structure of immunoglobulin G (IgG). Current methods to evaluate potential conjugation sites are time-consuming and labor intensive, involving multistep processes for individually produced reactions. Here, we describe a highly efficient method for identification of conjugatable genetic variants by analyzing pooled ADC libraries using mass spectrometry. This approach provides a versatile platform to rapidly uncover new conjugation sites for site-specific ADCs.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2020 Tipo de documento: Article