1. Academic Validation
  2. Imaging mass spectrometry for the precise design of antibody-drug conjugates

Imaging mass spectrometry for the precise design of antibody-drug conjugates

  • Sci Rep. 2016 Apr 21;6:24954. doi: 10.1038/srep24954.
Yuki Fujiwara 1 2 Masaru Furuta 3 Shino Manabe 4 Yoshikatsu Koga 1 Masahiro Yasunaga 1 2 Yasuhiro Matsumura 1 2
Affiliations

Affiliations

  • 1 Division of Developmental Therapeutics, Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Chiba, 277-8577, Japan.
  • 2 Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Chiba, 277-8561, Japan.
  • 3 Analytical &Measuring Instruments Division Shimadzu Corporation, Kyoto, 604-8511, Japan.
  • 4 Synthetic Cellular Chemistry Laboratory, RIKEN, Wako, Saitama, 351-0198, Japan.
Abstract

Antibody-drug conjugates (ADCs) are a class of immunotherapeutic agents that enable the delivery of cytotoxic drugs to target malignant cells. Because various cancers and tumour vascular endothelia strongly express anti-human tissue factor (TF), we prepared ADCs consisting of a TF-specific monoclonal antibody (mAb) linked to the Anticancer agent (ACA) monomethyl Auristatin E (MMAE) via a valine-citrulline (Val-Cit) linker (human TF ADC). Identifying the most efficient drug design in advance is difficult because ADCs have complicated structures. The best method of assessing ADCs is to examine their selectivity and efficiency in releasing and distributing the ACA within tumour tissue. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) can be used to directly detect the distributions of native molecules within tumour tissues. Here, MALDI-IMS enabled the identification of the intratumour distribution of MMAE released from the ADC. In conclusion, MALDI-IMS is a useful tool to assess ADCs and facilitate the optimization of ADC design.

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