Indication

Target/marker/pathway

Summary

Licensing status

Publication and contact information

Cancer

Acute myelogenous leukemia (AML)

Toll-like receptor 9
(TLR9); signal transducer and activator of transcription 3 (STAT3)

Mouse studies suggest simultaneously activating TLR9 and inhibiting STAT3 could help treat AML. In a mouse model of AML, a CpG-siRNA conjugate containing a Tlr9-stimulating CpG oligonucleotide and a Stat3-specific siRNA decreased tumor cell burden in blood, bone marrow, spleen and lymph nodes by 70%-80%, whereas a CpG-luciferase siRNA control reduced tumor cell burden by 30%. In the same model, the CpG-siRNA conjugate promoted antitumor immunity by increasing AML-induced CD8+ T cell infiltration and activation compared with CpG-luciferase siRNA. Next steps include testing more stable serum nuclease-resistant oligonucleotides in mouse models.

SciBX 6(48); doi:10.1038/scibx.2013.1375
Published online Dec. 19, 2013

Patent covering CpG-siRNA conjugates and their application to cancer and other immune-related diseases held by City of Hope; available for licensing

Hossain, D.M.S. et al. Blood;
published online Oct. 29, 2013;
doi:10.1182/blood-2013-07-517987
Contact: Marcin Kortylewski,
Beckman Research Institute at City of Hope, Duarte, Calif.
e-mail:
mkortylewski@coh.org
Contact: Ya-Huei Kuo, same affiliation as above
e-mail:
ykuo@coh.org