| Autor: |
Matsuda Y; Ajinomoto Bio-Pharma Services , 11040 Roselle Street , San Diego , California 92121 , United States., Robles V; Ajinomoto Bio-Pharma Services , 11040 Roselle Street , San Diego , California 92121 , United States., Malinao MC; Phenomenex, Inc. , 411 Madrid Avenue , Torrance , California 90501 , United States., Song J; Phenomenex, Inc. , 411 Madrid Avenue , Torrance , California 90501 , United States., Mendelsohn BA; Ajinomoto Bio-Pharma Services , 11040 Roselle Street , San Diego , California 92121 , United States. |
| Abstrakt: |
Antibody-drug conjugates (ADCs) have become a major class of oncology biopharmaceuticals. Traditional ADCs have a stochastic distribution of cytotoxic drugs attached at several different sites on the antibody. The heterogeneous nature of stochastic ADCs results in a complex compositional analysis. To improve on traditional ADC technology, we have developed a chemical conjugation platform termed "AJICAP" for the site-specific modification of native antibodies using a class of IgG Fc affinity reagents. Here we report further investigation focusing on several analyses of a first-generation AJICAP-ADC ( Angew. Chem., Int. Ed. 2019 , 58 , 5592-5597). For drug-antibody ratio (DAR) determination, we examined and compared six different analytical methods. To the best of our knowledge, this is the first report of a comparison of analytical techniques to measure the DAR for ADCs produced by a site-specific technology such as AJICAP. Furthermore, a rapid analytical process for confirmation of the site selectivity of AJICAP conjugation was established by SEC-Q-TOF-MS. The analytical strategy reported here can be applied to the DAR determination of site-specific ADCs. |
