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CTLA-4 (CD152); signal transducer and activator of transcription 3 (STAT3)

In vitro and mouse studies suggest a CTLA-4-binding aptamer linked to STAT3 siRNA could help treat cancer. An aptamer was designed that binds to Ctla-4
and is linked to Stat3 siRNA. In mouse models of melanoma, colorectal cancer, lymphoma and renal cell carcinoma, the aptamer-siRNA conjugate increased antigen-specific antitumor immunity and decreased tumor growth compared with a control aptamer-siRNA conjugate or vehicle. Next steps include clinical development of the aptamer-siRNA conjugate.
Bristol-Myers Squibb Co. markets the CTLA-4 mAb Yervoy ipilimumab to treat melanoma.
At least two other companies have therapeutics targeting CTLA-4 in Phase II or earlier testing.
Isis Pharmaceuticals Inc. and AstraZeneca plc have ISIS-STAT3Rx, an antisense oligonucleotide targeting STAT3, in Phase I/II testing to treat cancer.

SciBX 7(27); doi:10.1038/scibx.2014.790
Published online July 17, 2014

Provisional patent filed; available for licensing

Herrmann, A. et al. J. Clin. Invest.; published online
June 2, 2014;
Contact: Hua Yu, City of Hope Comprehensive Cancer Center, Duarte, Calif.