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CTLA-4 (CD152); inducible T cell co-stimulator (ICOS)

Mouse studies suggest combining anti-CTLA-4 antibodies plus vaccines that increase ICOS could help treat various cancers. In a mouse model of melanoma, inhibition of Ctla-4 increased expression of Icos on intratumoral T cells compared with no inhibition. In mice, an anti-Ctla-4 mAb plus a tumor cell vaccine made from irradiated melanoma cells expressing an Icos ligand resulted in an antitumor response that prevented melanoma tumor establishment after secondary challenge and caused a fourfold increase in rejection of intradermal melanoma tumors compared with anti-Ctla-4 mAb alone. The combined strategy also caused rejection of prostate tumors in mice. Next steps could include identifying other therapeutic methods to increase ICOS signaling.
Bristol-Myers Squibb Co. markets the anti-CTLA-4 mAb Yervoy ipilimumab to treat melanoma.
At least three other companies have CTLA-4-targeted agents in Phase II or earlier testing to treat various cancers.

SciBX 7(17); doi:10.1038/scibx.2014.483
Published online May 1, 2014

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Fan, X. et al. J. Exp. Med.; published online March 31, 2014;
Contact: James P. Allison, The University of Texas MD Anderson Cancer Center, Houston, Texas
Contact: Padmanee Sharma, same affiliation as above