Thursday, September 5, 2013
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Small molecules that
prevent teratoma formation in human pluripotent stem cell-derived therapies
Small molecules that are
selectively toxic to human pluripotent stem cells could help decrease the
tumorigenicity risk of stem cell-derived therapies. Residual,
undifferentiated stem cells in stem cell-derived cell therapies can lead to
teratoma formation. In mixed cultures of differentiated human cells and
undifferentiated human stem cells, small molecule inhibitors of survivin
such as sepantronium,
and small molecule inhibitors of B cell CLL lymphoma 10 (BCL10)
selectively induced apoptosis in undifferentiated cells. In a mixture of
differentiated human cells and undifferentiated human stem cells injected
into mice, none of the cell mixtures pretreated with sepantronium or another
small molecule survivin inhibitor developed teratomas, whereas all the
untreated cell mixtures did. Next steps include developing more specific
inhibitors of survivin and BCL10.
Pharma Inc.'s sepantronium, a survivin expression
inhibitor, is in Phase II testing to treat non-Hodgkin's lymphoma (NHL).
Pharmaceutical LLC's Terameprocol
nordihydroguaiaretic acid, a small molecule inhibitor of the
production and activation of survivin, is in Phase I for multiple cancers.
Published online Sept. 5, 2013
Patent application filed;
unavailable for licensing
Lee, M-.O. et al. Proc.
Natl. Acad. Sci. USA; published online Aug. 5, 2013;
Contact: Hyuk-Jin Cha, Sogang University, Seoul, South Korea
Contact: Kwang-Soo Kim, Harvard Medical School, Boston,
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