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Targeting soluble CD146 with a neutralizing antibody inhibits vascularization, growth and survival of CD146-positive tumors.

CD146 (MUC-18, MCAM) expression on cancer cells correlates with cancer progression and a bad prognosis in several tumors, including melanoma and pancreatic tumors. Deciphering the mechanism mediating the CD146 role in cancer is essential for generating new therapeutic strategies. We found that CD146 expression in cancer cells is associated with a secretion of soluble CD146 (sCD146) that constitutes an active player in tumor development. Indeed, sCD146 induces the overexpression of its binding protein, angiomotin, on both endothelial and cancer cells and promotes both paracrine effects on angiogenesis and autocrine effects on cancer cells proliferation and survival. These last effects are mediated in part through the induction and phosphorylation of c-myc in cancer cells. In mice models xenografted with human CD146-positive melanoma or pancreatic cancer cells, administration of a novel monoclonal antibody specifically targeting sCD146, but not its membrane form, successfully suppresses tumor vascularization and growth. Our findings demonstrate that sCD146 secreted by CD146-positive tumors mediates important pro-angiogenic and pro-tumoral effects. Targeting sCD146 with a novel neutralizing antibody could thus constitute an innovative therapeutic strategy for the treatment of CD146-positive tumors.Oncogene advance online publication, 11 April 2016; doi:10.1038/onc.2016.83.

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Cost-effectiveness of currently recommended direct-acting antiviral treatments in patients infected with genotypes 1 or 4 hepatitis C virus in the United States.

This study compared the cost-effectiveness of direct-acting antiviral therapies currently recommended for treating genotypes (GT) 1 and 4 chronic hepatitis C (CHC) patients in the United States (US).
A cost-effectiveness analysis of treatments for CHC from a US payer’s perspective over a lifelong time horizon was performed. A Markov model based on the natural history of CHC was used for a population that included treatment-naïve and -experienced patients. Treatment alternatives considered for GT1 included ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (3D±R), sofosbuvir + ledipasvir (SOF/LDV), sofosbuvir + simeprevir (SOF+SMV), simeprevir + pegylated interferon/ribavirin (SMV+PR), and no treatment (NT). For GT4 treatments were ombitasvir/paritaprevir/ritonavir + ribavirin (2D+R), SOF/LDV, and NT were compared. Transition probabilities, utilities, and costs were obtained from published literature. Outcomes included rates of compensated cirrhosis (CC), decompensated cirrhosis (DCC), hepatocellular carcinoma (HCC) and liver-related death (LrD), total costs, life-years, quality-adjusted life-years (QALYs). Costs and QALYs were used to calculate incremental cost-effectiveness ratios.
In GT1 patients, 3D±R and SOF-containing regimens have similar long term outcomes; 3D±R had the lowest lifetime risks of all liver disease outcomes: CC 30.2%, DCC 5.0%, HCC 6.8%, LT 1.9% and LrD 9.2%. In GT1 patients, 3D±R had the lowest cost and the highest QALYs. As a result, 3D±R dominated these treatment options. In GT4 patients, 2D+R had lower rates of liver morbidity and mortality, lower cost, and more QALYs than SOF/LDV and NT.
While the results are based on input values, which were obtained from a variety of heterogeneous sources – including clinical trials, the findings were robust across a plausible range of input values as demonstrated in probabilistic sensitivity analyses.
Among currently recommended treatments for GT1 and GT4 in the US, 3D±R (for GT1) and 2D+R (for GT4) have a favorable cost-effectiveness profile.

Systematic review of efficacy of anti-tumor necrosis factor (TNF) therapy in patients with psoriasis previously treated with a different anti-TNF agent.

Tumor necrosis factor (TNF) antagonists have improved outcomes for patients with psoriasis, but some patients are unresponsive to treatment (primary failure) or lose an initially effective response (secondary failure).
We sought to systematically investigate the efficacy and safety of a second TNF antagonist after failure of a first TNF antagonist.
Published primary studies evaluating the efficacy of switching TNF antagonists after failure were systematically extracted.
Fifteen studies were included. Although response rates to a second TNF antagonist were lower than for a first, a substantial proportion of patients in every study achieved treatment success. Week-24 response rates for a second antagonist were 30% to 74% for a 75% improvement in Psoriasis Area and Severity Index score and 20% to 70% for achieving a Physician Global Assessment score of 0/1; mean improvements in Dermatology Life Quality Index ranged from -3.5 to -13. In general, patients who experienced secondary failure achieved better responses than patients with primary failure. Adverse event incidences ranged from 20% to 71%, without unexpected adverse events; 0% to 11% of patients experienced serious adverse events.
There was no common definition of treatment failure across these studies of varied design.
Some patients benefit from switching to a second TNF antagonist after failure of a first TNF antagonist, with improved quality of life.
Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

8-K – Current report

On April 12, 2016 Adamis Pharmaceuticals Corporation (NASDAQ: ADMP) ("Company" or "Adamis") reported that it has successfully completed its previously announced acquisition (the "Acquisition") of US Compounding, Inc. ("USC") (Filing, 8-K, Adamis Pharmaceuticals, APR 12, 2016, View Source [SID:1234510680]). Upon the closing of this transaction, USC has become a wholly-owned subsidiary of Adamis.

Dr. Dennis J. Carlo, President and CEO of Adamis, stated, "We are pleased to have completed this transformational acquisition that will expand our product portfolio, provide immediate revenues, as well as significantly increase our manufacturing, sales and marketing capabilities. The combination will now position us to better commercialize our pipeline products upon approval and diversify our revenue mix.
Our Epinephrine Pre-filled Syringe ("PFS") has an FDA agency action date (PDUFA date) of June 4, 2016. The potential revenues from the PFS combined with the anticipated cash flows from USC, should put Adamis in a strong financial position."

Please see Adamis’ Form 8K filed with the Securities and Exchange Commission for additional details on the transaction.

Heat Biologics to Present at the American Association for Cancer Research (AACR) Annual Meeting

On April 12, 2016 Heat Biologics, Inc. ("Heat") (Nasdaq:HTBX), an immuno-oncology company developing novel therapies that activate a patient’s immune system against cancer, reported three poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting, including initial preclinical results from Heat’s collaboration with OncoSec Medical Incorporated, a biotechnology company developing DNA-based intra-tumoral cancer immunotherapies (Press release, Heat Biologics, APR 12, 2016, View Source [SID:1234510679]). The AACR (Free AACR Whitepaper) Annual Meeting is being held on April 16-20, 2016 in New Orleans, LA.

The details for the poster presentations at the AACR (Free AACR Whitepaper) Annual Meeting are as follows:

Title: In vivo intra-tumoral electroporation of Gp96-Ig/Fc-OX40L stimulates CD8+ T cell cross-priming to tumor specific neoantigens
Date and Time: April 17, 2016 at 1:00 p.m. – 5:00 p.m. CT
Location: Section 26
Session Title: Immune Modulating Agents 1
Abstract ID: 567

Title: Vesigenurtacel-L stimulates tumor infiltration of unique polyclonal T cell clones in non-muscle invasive bladder cancer patients
Date and Time: April 18, 2016 at 8:00 a.m. – 12:00 p.m. CT
Location: Section 22
Session Title: Immune Response Monitoring: Clinical
Abstract ID: 1405

Title: Combination immunotherapy: T cell costimulation (OX40L, TL1A, 4-1BBL and ICOSL) secreted locally by Gp96-Ig vaccines, elicits robust antigen-specific, memory T cell responses and tumor elimination
Date and Time: April 18, 2016 at 1:00 – 5:00 p.m. CT
Location: Section 27
Session Title: Therapeutic Antibodies and Vaccines
Abstract ID: 2353

Copies of the abstracts are available and can be viewed online through the AACR (Free AACR Whitepaper) website at www.aacr.org. Posters will be uploaded to the Publications section of Heat’s corporate website upon completion of the sessions to abide by the conference’s embargo policy.