Friday, December 19, 2014

Experimental drug works best when patients' immune cells surrounding tumors express PD-L1

A promising experimental immunotherapy drug works best in patients whose immune defenses initially rally to attack the cancer but then are stymied by a molecular brake that shuts down the response, according to a new study led by researchers at Dana-Farber Cancer Institute and the Yale University School of Medicine.

The antibody drug, known as MPDL3280A, inhibits the brake protein, PD-L1, reviving the response by immune killer T cells, which target and destroy the cancer cells. In recent clinical trials, the PD-L1 checkpoint blocker caused impressive shrinkage of kidney, melanoma, and lung tumors. But, as with other immunotherapy drugs, many patients saw no benefit.

Researchers report in the November 27 edition of Nature that the antibody was most effective when the patients' immune cells surrounding tumors expressed PD-L1 - a sign that a pre-existing immune response had been shut down by PD-L1. There was less tumor shrinkage in patients who never developed an immune response to the cancer - and, as a result, had less PD-L1 in the cancer and surrounding tissues.

"I think this is a launching point to use these findings as a predictive biomarker," said F. Stephen Hodi, MD, of Dana-Farber, senior author of the report. Hodi directs the Center for Immuno-Oncology and the Melanoma Treatment Center at Dana-Farber. First author is Roy Herbst, MD, PhD, chief of Medical Oncology at the Yale Comprehensive Cancer Center.

The scientists studied tumor tissue samples from 175 patients treated in clinical trials with MPDL3280A for advanced non-small cell lung cancer, melanoma, kidney cancer, and other cancers. On average, 18 percent of the patients had complete or partial shrinkage of their tumors, with higher or lower rates in different cancer types. Overall, the treatment was well-tolerated, with few severe side-effects, the report said.

Ref : http://meetinglibrary.asco.org/content/83740?media=vm

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