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

Yuki Fujiwara, Masaru Furuta, Shino Manabe, Yoshikatsu Koga, Masahiro Yasunaga, Yasuhiro Matsumura

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)

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.

Original languageEnglish
Article number24954
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Apr 21
Externally publishedYes

ASJC Scopus subject areas

  • General

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