國家衛生研究院 NHRI:Item 3990099045/12351

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Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/12351

Title:	Inhibition of Rspo-Wnt pathway facilitates checkpoint blockade therapy by anti-RSPO3 antibody (DBPR117)
Authors:	Hsu, JTA;Hung, HC;Chen, CT;Yen, WC;Chang, TY;Chao, PK;Chin-Ting, H;Yen, KJ;Tsai, YR;Chang, CY;Fang, MY;Lai, YL;Shih, JC
Contributors:	Institute of Biotechnology and Pharmaceutical Research
Abstract:	Background: PD-1/PD-L1 antibody can be effective on less than 30-40% of solid tumors. It is urgent to find new targets or combining therapies to broaden the patient populations so that more cancer patients can be successfully treated by PD-1/PD-L1 checkpoint blockade inhibition. Recent studies supported that targeting Wnt/b-Catenin signaling would increase anti-cancer immune evasion response through regulation of immune cell infiltration within the tumor microenvironment. Several lines of evidence have revealed that the family members of R-spondins (RSPOs) can mediate with Lgr4 or Lgr5 proteins/Frizzled/LRP receptor complexes as an independent (noncanonical) control of the Wnt pathway. Multiple cancer types were found to bear aberrant RSPO3/Wnt signaling. Methods: In this study, we have identified an anti-RSPO3 antibody (DBPR117) as shown in a variety of assays including the lignad binding assays, in vitro bioassays, in vivo PDX (patient-derive xenograft), and mouse syngeneic models. DBPR117 is capable of binding and neutralizing human as well as murine RSPO3 in cell culture. Results: Dependent on the cancer types, effective tumor growth inhibition in vivo can be achieved by administration by DBPR117 alone, or in combination with an anti-PD1 antibody. The interplays of RSPO3 and PD1 on tumor growth and metastases will be elucidated and discussed. How the findings in the laboratory may be translated into clinics will also be presented. Conclusions: Additional studies are warranted to evaluate how DBPR117, a novel anti-RSPO3 humanized antibody, may be translated into clinical applications.
Date:	2019-10
Relation:	Annals of Oncology. 2019 Oct;30(Suppl. 5):191.
Link to:	https://doi.org/10.1093/annonc/mdz244.070
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0923-7534&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000491295501325
Appears in Collections:	[Wan-Ching Yen] Conference Papers/Meeting Abstract [Chiung-Tong Chen] Conference Papers/Meeting Abstract [John Tsu-An Hsu] Conference Papers/Meeting Abstract [Chuan Shih(2014-2017)] Conference Papers/Meeting Abstract

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