Efficacy studies of an antibody-drug conjugate PSMA-ADC in patient-derived prostate cancer xenografts

The Prostate ◽  
2014 ◽  
Vol 75 (3) ◽  
pp. 303-313 ◽  
Author(s):  
Vincent A. DiPippo ◽  
William C. Olson ◽  
Holly M. Nguyen ◽  
Lisha G. Brown ◽  
Robert L. Vessella ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Efficacy Studies ◽  
Antibody Drug

A phase I study of DSTP3086S, an antibody-drug conjugate (ADC) targeting STEAP-1, in patients (pts) with metastatic castration-resistant prostate cancer (CRPC).

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 5024-5024 ◽  
Author(s):  
Daniel Costin Danila ◽  
Russell Zelig Szmulewitz ◽  
Ari David Baron ◽  
Celestia S. Higano ◽  
Howard I. Scher ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Phase I Study ◽  
Castration Resistant Prostate Cancer ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Castration Resistant ◽  
Antibody Drug

Preclinical efficacy studies using HuMax-Axl-ADC, a novel antibody-drug conjugate targeting Axl-expressing solid cancers.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 3066-3066 ◽  
Author(s):  
Esther CW Breij ◽  
Sandra Verploegen ◽  
Andreas Lingnau ◽  
Edward N van den Brink ◽  
Maarten Janmaat ◽  
...  
Keyword(s):  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Preclinical Efficacy ◽  
Efficacy Studies ◽  
Antibody Drug

STEAP1 as a predictive biomarker for antibody-drug conjugate (ADC) activity in metastatic castration resistant prostate cancer (mCRPC).

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Daniel Costin Danila ◽  
Martin Fleisher ◽  
Jorge A. Carrasquillo ◽  
Houston Gilbert ◽  
Michael J. Morris ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Predictive Biomarker ◽  
Castration Resistant Prostate Cancer ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Castration Resistant ◽  
Antibody Drug

Rovalpituzumab tesirine (Rova-T) as a therapeutic agent for Neuroendocrine Prostate Cancer (NEPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 5029-5029 ◽  
Author(s):  
Loredana Puca ◽  
Verena Sailer ◽  
Kaitlyn Gayvert ◽  
Kumiko Isse ◽  
Michael Sigouros ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Surface ◽  
Cell Lines ◽  
Therapeutic Agent ◽  
Cellular Proliferation ◽  
Prostate Adenocarcinoma ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Castration Resistant ◽  
Antibody Drug

5029 Background: TheNotch ligand Delta like ligand 3 (DLL3) is aberrantly expressed on the cell surface of small cell lung cancer (SCLC), and the DLL3-antibody drug conjugate, Rova-T, has shown promise for patients with SCLC (Rudin et al, Lancet Onc 2017). NEPC is a late stage subtype of castration resistant prostate cancer with limited therapeutic options. Based on clinical and molecular similarities with SCLC, we investigated expression of DLL3 and the use of Rova-T in NEPC. Methods: We evaluated mRNA and/or protein expression of DLL3 in a cohort of 395 patients (535 samples) ranging from benign prostate (BEN), localized prostate adenocarcinoma (PCA), castration resistant adenocarcinoma (CRPC), and NEPC and correlated with pathologic and genomic features. Prostate cancer cell lines and patient-derived organoids were treated with Rova-T (SC16LD6.5) in vitro and in vivo. Results: DLL3 was expressed at the mRNA and/or protein level in 0/143 BEN (0%), 4/266 PCA (1%), 8/76 CRPC (10%), 33/50 NEPC (66%). DLL3 IHC was of higher intensity in NEPC and co-localized with classical NE marker expression (SYP, CGA). DLL3 was amongst the most differentially expressed genes by RNA-seq in NEPC versus CRPC (p = < 0.0001, fold change = 71), correlated with ASCL1 expression (r = 0.88) and RB1 genomic loss (83%), and inversely with AR expression. Although treatment with the Notch inhibitor DAPT suppressed Notch target gene expression in NEPC, DAPT did not have significant effect on cellular proliferation. siRNA knockdown of DLL3 or DAPT did not alter AR signaling or NE markers. Rova-T (SC16LD6.5) was active in DLL3-positive NEPC cell lines with an IC50 of 580pM compared to the control IgG1LD6.5 (IC50 = 6.3nM), whereas CRPC lines were insensitive. Conclusions: DLL3 is a cell surface protein aberrantly expressed in the majority of NEPC and a subset of CRPC, and is not expressed in primary prostate cancer or benign tissues. The DLL3 antibody-drug conjugate Rova-T demonstrates preferential preclinical activity in NEPC compared to prostate adenocarcinoma. These data support further investigation of Rova-T as a potential therapeutic agent for NEPC. A phase I trial with dedicated NEPC arm is currently accruing patients (NCT02709889).

Phase 1 study of PSMA ADC, an antibody‐drug conjugate targeting prostate‐specific membrane antigen, in chemotherapy‐refractory prostate cancer

The Prostate ◽  
2019 ◽  
Vol 79 (6) ◽  
pp. 604-613 ◽  
Author(s):  
Daniel P. Petrylak ◽  
Philip Kantoff ◽  
Nicholas J. Vogelzang ◽  
Anthony Mega ◽  
Mark T. Fleming ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase 1 ◽  
Prostate Specific Membrane Antigen ◽  
Antibody Drug Conjugate ◽  
Phase 1 Study ◽  
Drug Conjugate ◽  
Specific Membrane ◽  
Antibody Drug

scholarly journals Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody–Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer

2018 ◽  
Vol 17 (10) ◽  
pp. 2176-2186 ◽  
Author(s):  
Song Cho ◽  
Francesca Zammarchi ◽  
David G. Williams ◽  
Carin E.G. Havenith ◽  
Noel R. Monks ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Antitumor Activity ◽  
Preclinical Models ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

Abstract 3620: LIV-1 antibody-drug conjugate: A novel therapeutic agent for breast and prostate cancer

2011 ◽  
Author(s):  
Django Sussman ◽  
Albina Nesterova ◽  
Lori Westendorf ◽  
Steven Duniho ◽  
Martha Anderson ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Therapeutic Agent ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Breast And Prostate Cancer ◽  
Antibody Drug ◽  
Novel Therapeutic
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