当前位置： SCI文献检索 > Theranostics期刊下所有文献 > Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer.

Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer.

Abstract：

:CUB-domain containing protein 1 (CDCP1) is a cancer associated cell surface protein that amplifies pro-tumorigenic signalling by other receptors including EGFR and HER2. Its potential as a cancer target is supported by studies showing that anti-CDCP1 antibodies inhibit cell migration and survival in vitro, and tumor growth and metastasis in vivo. Here we characterize two anti-CDCP1 antibodies, focusing on immuno-conjugates of one of these as a tool to detect and inhibit ovarian cancer. Methods: A panel of ovarian cancer cell lines was examined for cell surface expression of CDCP1 and loss of expression induced by anti-CDCP1 antibodies 10D7 and 41-2 using flow cytometry and Western blot analysis. Surface plasmon resonance analysis and examination of truncation mutants was used to analyse the binding properties of the antibodies for CDCP1. Live-cell spinning-disk confocal microscopy of GFP-tagged CDCP1 was used to track internalization and intracellular trafficking of CDCP1/antibody complexes. In vivo, zirconium 89-labelled 10D7 was detected by positron-emission tomography imaging, of an ovarian cancer patient-derived xenograft grown intraperitoneally in mice. The efficacy of cytotoxin-conjugated 10D7 was examined against ovarian cancer cells in vitro and in vivo. Results: Our data indicate that each antibody binds with high affinity to the extracellular domain of CDCP1 causing rapid internalization of the receptor/antibody complex and degradation of CDCP1 via processes mediated by the kinase Src. Highlighting the potential clinical utility of CDCP1, positron-emission tomography imaging, using zirconium 89-labelled 10D7, was able to detect subcutaneous and intraperitoneal xenograft ovarian cancers in mice, including small (diameter <3 mm) tumor deposits of an ovarian cancer patient-derived xenograft grown intraperitoneally in mice. Furthermore, cytotoxin-conjugated 10D7 was effective at inhibiting growth of CDCP1-expressing ovarian cancer cells in vitro and in vivo. Conclusions: These data demonstrate that CDCP1 internalizing antibodies have potential for killing and detection of CDCP1 expressing ovarian cancer cells.

journal_name

Theranostics

journal_title

Theranostics

authors

Harrington BS,He Y,Khan T,Puttick S,Conroy PJ,Kryza T,Cuda T,Sokolowski KA,Tse BW,Robbins KK,Arachchige BJ,Stehbens SJ,Pollock PM,Reed S,Weroha SJ,Haluska P,Salomon C,Lourie R,Perrin LC,Law RHP,Whisstock JC,Hoop

doi

10.7150/thno.30736

subject

Has Abstract

pub_date

2020-01-12 00:00:00

pages

2095-2114

issue

issn

1838-7640

pii

thnov10p2095

journal_volume

pub_type

杂志文章

在线工具

Anti-CDCP1 immuno-conjugates for detection and inhibition of ovarian cancer.