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.
Resources from the same session
3336 - Survival outcome of non-small cell lung cancer (NSCLC) patients: Comparing results between the database of the Comprehensive Cancer Center Zürich (CCCZ) and the Epidemiological Cancer Registry Zurich and Zug (KKR)
Presenter: Rolf A. Stahel
Session: Poster Display session 1
Resources:
Abstract
2204 - NORA trial (GECP 15/02): Updated results of the Spanish Lung Cancer Group (SLCG) phase II trial of concurrent chemo-radiotherapy (CT-RT) with cisplatin (P) plus metronomic oral vinorelbine (mOV) for unresectable locally advanced non-small cell lung cancer (LA-NSCLC)
Presenter: María Guirado
Session: Poster Display session 1
Resources:
Abstract
1446 - A nomogram to predict outcomes of lung cancer patients after pneumonectomy based on 47 indicators set by principle component analysis
Presenter: Bo Cheng
Session: Poster Display session 1
Resources:
Abstract
1788 - Prognostic and predictive value of 18F-PET/CT on the response to treatment in locally advanced non-small cell lung cancer (NSCLC)
Presenter: Cristina Alfaro Autor
Session: Poster Display session 1
Resources:
Abstract
2299 - Comparison of three different chemotherapy regimens for concomitant chemoradiotherapy in locally advanced non small cell lung cancer
Presenter: Abdurrahman Işıkdoğan
Session: Poster Display session 1
Resources:
Abstract
4211 - Predicting the first failure pattern in patients with inoperable local advanced non-small cell lung cancer (LA-NSCLC) receiving definitive chemoradiotherapy: Establishment and internal validation of a nomogram based on the clinicopathological factors
Presenter: Xueru Zhu
Session: Poster Display session 1
Resources:
Abstract
1550 - Prognostic impact of neutrophil-to-lymphocyte ratio (NLR) pre and post chemoradiotherapy (CRT) in stage III non-small cell lung cancer (NSCLC)
Presenter: Vicente Palomar Abril
Session: Poster Display session 1
Resources:
Abstract
2345 - Meta-analysis evaluating neutropenia incidence with EGFR inhibitors and chemotherapy in patients with NSCLC
Presenter: Bernardo Rapoport
Session: Poster Display session 1
Resources:
Abstract
3747 - Effector CD4+ T-cell induction by thoracic radiotherapy for patients with NSCLC
Presenter: Yu Miura
Session: Poster Display session 1
Resources:
Abstract
3317 - Circulating tumor DNA (ctDNA) analysis in patients (pts) with non-small cell lung cancer (NSCLC) treated with telisotuzumab vedotin (teliso-v), an antibody-drug conjugate targeting c-Met
Presenter: Rebecca Heist
Session: Poster Display session 1
Resources:
Abstract