演題概要

2P-30

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Native SEC-MSを用いた薬物抗体比（DAR）評価系の最適化検討

(アステラス製薬)
^o中江隆豊・ 草間大志・ 三村真大・ 平倉穣

Antibody-drug conjugates (ADCs) are one of the important modalities in cancer treatments. ADCs consist of a monoclonal antibody (mAb) attached to drugs via linkers. The potency of ADCs primarily depends on the drug to antibody ratio (DAR), which refers to the average number of drugs bound to the mAb. DAR is therefore considered as one of the critical quality attributes (CQA) of ADCs. To perform the analysis in native conditions, size-exclusion chromatography with mass spectrometry (SEC-MS) is one of the promising methods. There are some difficulties in accurately determining DAR using SEC-MS. Here, we investigated various MS measurement parameters to accurately determine DAR by performing SEC-MS measurements while maintaining the ADC structure. We identified vaporizer temperature as a critical parameter to maintain the structure during SEC-MS measurements. Other MS measurement parameters affected the peak intensity but not the structure of the ADC. Next, various ADCs were prepared by conjugating several types of mAbs and DLs in each combination. The prepared ADCs were measured by SEC-MS and the effect of glycan digestion and differences in analysis methods were evaluated from the obtained DAR values. Under optimized conditions, which allow us to obtain simpler mass spectra, DAR values can be measured more robustly.