Repository logo
 
Publication

Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast Cancer

2021Journal article Open access
Simple item page
dc.contributor.authorSilva, G
dc.contributor.authorSales-Dias, J
dc.contributor.authorCasal, D
dc.contributor.authorAlves, S
dc.contributor.authorDomenici, G
dc.contributor.authorBarreto, C
dc.contributor.authorMatos, C
dc.contributor.authorLemos, A
dc.contributor.authorMatias, A
dc.contributor.authorKucheryava, K
dc.contributor.authorFerreira, A
dc.contributor.authorMoita, MR
dc.contributor.authorBraga, S
dc.contributor.authorBrito, C
dc.contributor.authorCabral, MG
dc.contributor.authorCasalou, C
dc.contributor.authorBarral, D
dc.contributor.authorSousa, P
dc.contributor.authorVideira, P
dc.contributor.authorBandeiras, T
dc.contributor.authorBarbas, A
dc.date.accessioned2021-10-13T15:00:39Z
dc.date.available2021-10-13T15:00:39Z
dc.date.issued2021
dc.description.abstractThe Notch-signaling ligand DLL1 has emerged as an important player and promising therapeutic target in breast cancer (BC). DLL1-induced Notch activation promotes tumor cell proliferation, survival, migration, angiogenesis and BC stem cell maintenance. In BC, DLL1 overexpression is associated with poor prognosis, particularly in estrogen receptor-positive (ER+) subtypes. Directed therapy in early and advanced BC has dramatically changed the natural course of ER+ BC; however, relapse is a major clinical issue, and new therapeutic strategies are needed. Here, we report the development and characterization of a novel monoclonal antibody specific to DLL1. Using phage display technology, we selected an anti-DLL1 antibody fragment, which was converted into a full human IgG1 (Dl1.72). The Dl1.72 antibody exhibited DLL1 specificity and affinity in the low nanomolar range and significantly impaired DLL1-Notch signaling and expression of Notch target genes in ER+ BC cells. Functionally, in vitro treatment with Dl1.72 reduced MCF-7 cell proliferation, migration, mammosphere formation and endothelial tube formation. In vivo, Dl1.72 significantly inhibited tumor growth, reducing both tumor cell proliferation and liver metastases in a xenograft mouse model, without apparent toxicity. These findings suggest that anti-DLL1 Dl1.72 could be an attractive agent against ER+ BC, warranting further preclinical investigation.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCancers (Basel). 2021 Aug 13;13(16):4074.pt_PT
dc.identifier.doi10.3390/cancers13164074.pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.17/3881
dc.language.isoengpt_PT
dc.publisherMDPIpt_PT
dc.relationPTDC/BBB-BMD/4497/2014/Fundação para a Ciência e a Tecnologiapt_PT
dc.relationPD/BD/113987/2015/Fundação para a Ciência e a Tecnologiapt_PT
dc.relationUIDP/04378/2020/Fundação para a Ciência e a Tecnologiapt_PT
dc.relationUIDB/04378/2020/Fundação para a Ciência e a Tecnologiapt_PT
dc.relation3D-ABC-PI-717/iBETXplore grantpt_PT
dc.subjectHSJ ANPATpt_PT
dc.subjectDLL1pt_PT
dc.subjectER+ Breast Cancerpt_PT
dc.subjectNotch Signalingpt_PT
dc.subjectAngiogenesispt_PT
dc.subjectCell Proliferationpt_PT
dc.subjectMonoclonal Antibodypt_PT
dc.subjectTumor Growth.pt_PT
dc.titleDevelopment of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast Cancerpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.citation.startPage4074pt_PT
oaire.citation.titleCancerspt_PT
oaire.citation.volume13pt_PT
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
cancers-13-04074.pdf
Size:
4.03 MB
Format:
Adobe Portable Document Format
Download

Collections

ANPAT - Artigos