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Poster Display session 1

5054 - Inhibition of Rspo-Wnt pathway Facilitates Checkpoint Blockade Therapy by anti-RSPO3 antibody (DBPR117)

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Clinical Research

Tumour Site

Presenters

John Hsu

Citation

Annals of Oncology (2019) 30 (suppl_5): v159-v193. 10.1093/annonc/mdz244

Authors

J.T. Hsu1, H. Hung2, C. Chen3, W. Yen3, T. Chang3, P. Chao1, H. Chin-Ting1, K. Yen3, Y. Tsai1, C. Chang1, M. Fang1, Y. Lai1, J.C. Shih1

Author affiliations

  • 1 Biotechnology And Pharmaceutical Research, National Health Research Institutes - Zhunan Campus, 35053 - Zhunan/TW
  • 2 Biotechnology And Pharmaceutical Research, National Health Research Institutes, 350 - Hunan/TW
  • 3 Biotechnology And Pharmaceutical Research, National Health Research Institutes, 350 - Zhunan/TW

Resources

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Abstract 5054

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.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Ministry of Health and Welfare.

Disclosure

All authors have declared no conflicts of interest.

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