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biopharm

04/07/17 5:58 AM

#294182 RE: spankyvol #294181

Data Mining is huge these days and Robert Mercer of Renaissance knows well of Peregrine Pharmaceuticals. I see a statistically significant number of pre-5AM posts very recently and another sign something is coming Peregrines way.... thank you!

JJ1223

04/07/17 12:34 PM

#294252 RE: spankyvol #294181

But I am sure there are a half dozen BPs with buckets of money at the front door of the PPer. Right?



Yes, you are probably right spanky. IMO, there may be as many as 25-30 companies testing PS Targeting with the hopes of improving the performance of their drug. We hear of more everyday. GLTA


Preclinical Evaluation of Sequential Combination of Oncolytic Adenovirus Delta-24-RGD and Phosphatidylserine-Targeting Antibody in Pancreatic Ductal Adenocarcinoma

Published April 2017

Bingbing Dai, David Roife, Ya'an Kang, Joy Gumin, Mayrim V. Rios Perez, Xinqun Li, Michael Pratt, Rolf A. Brekken, Juan Fueyo-Margareto, Frederick F. Lang, and Jason B. Fleming

Quote:

Abstract

Delta-24-RGD (DNX-2401) is a conditional replication-competent oncolytic virus engineered to preferentially replicate in and lyse tumor cells with abnormality of p16/RB/E2F pathway. In a phase I clinical trial, Delta-24-RGD has shown favorable safety profile and promising clinical efficacy in brain tumor, which prompted us to evaluate its anticancer activity in pancreatic ductal adenocarcinoma (PDAC), which also has high frequency of homozygous deletion and promoter methylation of CDKN2A encoding the p16 protein. Our results demonstrate that Delta-24-RGD can induce dramatic cytotoxicity in a subset of PDAC cell lines with high cyclin D1 expression. Induction of autophagy and apoptosis by Delta-24-RGD in sensitive PDAC cells was confirmed with LC3B-GFP autophagy reporter and acridine orange staining as well as Western blotting analysis of LC3B-II expression. Notably, we found that Delta-24-RGD induced phosphatidylserine exposure in infected cells independent of cells' sensitivity to Delta-24-RGD, which renders a rationale for combination of Delta-24-RGD viral therapy and phosphatidylserine targeting antibody for PDAC. In a mouse PDAC model derived from a liver metastatic pancreatic cancer cell line, Delta-24-RGD significantly inhibited tumor growth compared with control (P < 0.001), and combination of phosphatidylserine targeting antibody 1N11 further enhanced its anticancer activity (P < 0.01) possibly through inducing synergistic anticancer immune responses. Given that these 2 agents are currently in clinical evaluation, our study warrants further clinical evaluation of this novel combination strategy in pancreatic cancer therapy. Mol Cancer Ther; 16(4); 662–70. ©2016 AACR.



http://mct.aacrjournals.org/content/16/4/662