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- Title
Induction of Immunogenic Cell Death by Chemotherapeutic Platinum Complexes.
- Authors
Wong, Daniel Yuan Qiang; Ong, Wendy Wei Fang; Ang, Wee Han
- Abstract
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 PtII 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.
- Subjects
IMMUNE response; TUMOR treatment; CELL death; PHAGOCYTOSIS; CARBENES
- Publication
Angewandte Chemie, 2015, Vol 127, Issue 22, p6583
- ISSN
0044-8249
- Publication type
Article
- DOI
10.1002/ange.201500934