Suzanne L. Topalian,Maria L. Ascierto,Drew M. Pardoll,Janis Taube
申请号：
US15510959
公开号：
US20170275705A1
申请日:
2015.09.15
申请国别(地区):
US
年份:
2017
代理人:
摘要：
PD-L1 expression by tumor cells prior to treatment correlates highly with response to anti-PD-1 and anti-PD-L1 therapy (e.g., nivolumab (Bristol-Myers Squibb), pembrolizumab (Merck)) and anti-PD-L1 monotherapy (MPDL3280A (Genentech/Roche)). Nonetheless, the majority of patients with PD-LI(+) tumors do not respond to PD-1 pathway blockade. Distinct gene profiles associated with differential response to treatment with an anti-PD-1 antibody in patients with PD-L1+ renal cell carcinoma have been identified. In particular, a strong up-regulation of genes involved in metabolic functions and pathways was found in patients not responding to the therapy. Additionally, a down-regulation of genes involved in cellular migration functions was found in the same group of patients (non-responders). Specific biomarkers can be used to stratify responders from non-responders for PD-1 pathway blocking drugs. Additionally, the biomarkers represent therapeutic targets for anti-PD-1 combination therapy, and companion diagnostic products for such combination therapies.
