Thursday, September 20, 2012
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Killer cell lectin-like receptor subfamily K member
ligands as markers to predict response to anti-CTLA-4
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.
Squibb Co. markets the human anti-CTLA-4 mAb Yervoy
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.
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).
Published online Sept. 20, 2012
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.
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