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Aug 09, 2012
 |  BC Innovations  |  Targets & Mechanisms

Screening for immunogenic cell death

French researchers have used a fluorescence-based screening platform to identify small molecules that induced immunogenic cell death in mouse tumors.1 Next, the group plans to test the best hits in a Phase I/II trial to treat locally invasive head and neck cancers in combination with chemotherapy.

In 2005, Guido Kroemer and colleagues first showed that the anthracycline chemotherapeutic doxorubicin could induce immune-mediated death of cancer cells in addition to the known process of cell death through DNA damage.2 The immunogenic process was later shown to be mediated by multiple factors involved in apoptosis and autophagy.3-6

Based on those mechanistic findings, Kroemer and colleagues decided to design an automated epifluorescence microscopy-based screening platform that could detect several hallmarks of immunogenic cell death and thus be used to identify new compounds that trigger this process in a human osteosarcoma cell line.

First, the researchers validated the new screening platform using a library of 120 marketed cancer therapies. Based on the readouts, the most potent compounds included several known inducers of immunogenic cell death, including doxorubicin, daunorubicin and mitoxantrone. Two other top hits were drugs known to have immunogenic side effects: vincristine and vinorelbine.

Next, the researchers used the platform to screen for new inducers of immunogenic cell death. Of the top 10 hits, 4 were small molecule cardiac glycosides, including digoxin and digitoxin, which are marketed to reduce arrhythmias in patients with...

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