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Induction of Immunogenic Cell Death by Chemotherapeutic Platinum Complexes
Author(s) -
Wong Daniel Yuan Qiang,
Ong Wendy Wei Fang,
Ang Wee Han
Publication year - 2015
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201500934
Subject(s) - immunogenic cell death , calreticulin , phagocytosis , endoplasmic reticulum , cytotoxicity , programmed cell death , immune system , inducer , in vitro , cancer research , cell , chemistry , biology , immunology , microbiology and biotechnology , apoptosis , immunotherapy , biochemistry , gene
There is compelling evidence suggesting that the immune‐modulating effects of many conventional chemotherapeutics, including platinum‐based agents, play a crucial role in achieving clinical response. One way in which chemotherapeutics can engage a tumor‐specific immune response is by triggering an immunogenic mode of tumor cell death (ICD), which then acts as an “anticancer vaccine”. In spite of being a mainstay of chemotherapy, there has not been a systematic attempt to screen both existing and upcoming Pt agents for their ICD ability. A library of chemotherapeutically active Pt agents was evaluated in an in vitro phagocytosis assay, and no correlation between cytotoxicity and phagocytosis was observed. A Pt II N‐heterocyclic carbene complex was found to display the characteristic hallmarks of a type II ICD inducer, namely focused oxidative endoplasmic reticulum (ER) stress, calreticulin exposure, and both HMGB1 and ATP release, and thus identified as the first small‐molecule immuno‐chemotherapeutic agent.