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Killer cell lectin-like receptor subfamily K member 1 (KLRK1; CD314; NKG2D) ligands as markers to predict response to anti-CTLA-4 (CD152) therapies and guide selection of radiation therapy regimens

Mouse studies suggest levels of NKG2D ligands could be used as a marker to predict patient responsiveness to anti-CTLA-4 therapies and help guide selection of radiation therapy regimens. In mice bearing poorly immunogenic tumors, an anti-CTLA-4 mAb plus radiotherapy led to greater T cell contact time with tumor cells and tumor regression than either therapy alone. In the xenograft mice treated with the combination therapy, an anti-NKG2D mAb reversed the increased T cell contact time and tumor regression, suggesting ligand-NKG2D interactions are required for anti-CTLA-4 and radiotherapy synergy. Next steps include clinical trials to determine the best radiation therapy regimens to use with anti-CTLA-4 therapies in patients with melanoma.
Bristol-Myers Squibb Co. markets the human anti-CTLA-4 mAb Yervoy ipilimumab to treat melanoma. The mAb also is in Phase III testing for prostate cancer and Phase II testing for lung cancer, non-small cell lung cancer (NSCLC), pancreatic cancer and solid tumors.
Pfizer Inc. and AstraZeneca plc have the human anti-CTLA-4 mAb tremelimumab in Phase II testing for liver cancer and solid tumors and in Phase I for melanoma and prostate cancer (see Strategic synergy, page 8).

SciBX 5(37); doi:10.1038/scibx.2012.993
Published online Sept. 20, 2012

Unpatented; unlicensed

Ruocco, M.G. et al. J. Clin. Invest.; published online Sept. 4, 2012;
Contact: Sandra Demaria,
New York University School of Medicine, New York, N.Y.