Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts
发明人:
Philipp Beckhove,Michael Boutros,Marco Breinig,Nisit Khandelwal,Tillmann Michels,Antonio Sorrentino,Valentina Volpin
申请号：
US16347397
公开号：
US20190263906A1
申请日:
2017.11.10
申请国别(地区):
US
年份:
2019
代理人:
摘要：
The present invention pertains to novel modulators of resistance against T-cell mediated cytotoxic immune responses. The invention provides antagonists of immune escape mechanisms and therefore offers a novel approach for treating, or aiding a treatment, of various proliferative diseases such as cancerous diseases, in particular melanoma, pancreatic cancer and colorectal cancer. The invention specifically discloses the receptor Olfactory Receptor, Family 10, Subfamily H, Member 1 (OR10H1)as a checkpoint molecule in tumor resistance against cytotoxic T-cells. Provided is the inhibition of OR10H1 expression and/or function as a strategy for enhancing tumor susceptibility to a patients T-cell mediated immune response. Provided are antigen binding constructs for the detection of the OR10H1 protein, as well as inhibitory compounds, such as siRNA/shRNA molecules targeting OR10H1 and anti-OR10H1 antibodies, forimpairing the immune escape mediated by OR10H1. The invention furthermore provides screening methods for the identification of novel cancer therapeutics based on the modulation OR10H1 expression/function, diagnostic methods for the detection of immune resistance of a tumor to cytotoxic T-cell responses, as well as pharmaceutical compositions and diagnostic kits for performing these methods.
