Came across this publication yesterday. I'm not saying Organovo is involved, but I do know we were part of the CCPD Collaborative Network with University of Nottingham, and also have partnered with Janssen Research and Development. Just some food for thought...
3-Dimensional Patient-Derived Lung Cancer Assays Reveal Resistance to Standards-of-Care Promoted by Stromal cells but Sensitivity to Histone Deacetylase Inhibitors.
There is a growing recognition that current pre-clinical models do not reflect the tumor microenvironment in cellular, biological and biophysical content and this may have a profound effect on drug efficacy testing especially in the era of molecular-targeted agents. Here we describe a method to directly embed low passage patient tumor-derived tissue into basement membrane extract, ensuring a low proportion of cell death to anoikis and growth complementation by co-culture with patient-derived cancer-associated fibroblasts (CAFs). A range of solid tumors proved amenable to growth and pharmacological testing in this 3D assay. A study of 30 early-stage non-small cell lung cancer (NSCLC) specimens revealed high levels of de novo resistance to a large range of standards-of-care agents, while histone deacetylase (HDAC) inhibitors and their combination with antineoplastic drugs displayed high levels of efficacy. Increased resistance was seen in the presence of patient-derived CAFs for many agents, highlighting the utility of the assay for tumor microenvironment-educated drug testing. Standard-of-care agents showed similar responses in the 3D ex vivo and patient-matched in vivo models validating the 3D-Tumor Growth Assay (3D-TGA) as a high-throughput screen for close-to-patient tumors using significantly reduced animal numbers.
Found this under their news section:
Leah Norona, graduate student in the lab of Dr. Ed LeCluyse at the Hamner Institutes is receiving support from OrganovoTM (ONVO) to pursue her doctoral dissertation aimed at understanding the mode of action underlying fibrogenic chemicals. Leah submitted a proposal outlining the utility of ONVO’s model system with which to clarify the early initiating and adaptive events during chemical-induced fibrosis and the role of the resident cell types in mediating the liver’s response to chronic insult. ONVO is an early stage biotech company which designs and develops multicellular, functional, and structurally relevant 3D human tissue using bio-printing technology. Recently, Leah spent three weeks at ONVO headquartered in San Diego, CA to learn more about the bio-printing process and conducted proof-of-concept studies using their exVive3DTM human liver tissue product. The results from this project will establish and characterize a prototype chemical-induced fibrotic injury response and foster a broader collaborative effort to better understand the impact of chemical exposure on the initiation and progression of liver injury and disease.
This is the same Leah Norona that will be presenting at the World Preclinical Congress on June 15th, 2016.
From the earnings call:
"Finally, we continue to see great promise for our tissue replacement products where the potential exists to revolutionize therapeutic applications and materially improve patient outcomes. We're still in the early days and are seeing solid result in animal models in the multiple tissue types that we're evaluating.
Our timelines are on course as we continue to aim for an investigational new drug or IND submission with the FDA in the next three to five years depending on the tissue type and expect to share preliminary data from the animal models in the next 12 months to 18 months."
NEW IN VITRO SCREENING APPROACHES FOR SAFETY TESTING
3:35 Combination of Screening Assays for Assessing Drug-Induced Liver Injury in Humans
Christoph Funk, Ph.D., Vice Director, Pharmaceutical Sciences, F. Hoffmann-La Roche
Drug-induced liver injury (DILI) is one of the leading causes for acute hepatic failure and drug withdrawal. The potential DILI risk can be identified early-on by assessing multiple endpoints contributing to human DILI (metabolic activation, cytotoxicity and transporter inhibition) in conjunction with compound exposure. The approach was validated using 125 marketed or withdrawn compounds with different degree for DILI and exhibited an overall sensitivity and specificity of 80 and 86%.
4:35 Generation of Complex Disease Phenotypes in 3D Bioprinted Human Liver Tissues for the Assessment of Drug-Induced Injury
Leah Norona, Doctoral Candidate Curriculum in Toxicology, University of North Carolina at Chapel Hill
Compound-induced hepatotoxicity leading to fibrosis remains a challenge for human risk assessment. Latency to detection and limitations of conventional model systems make it difficult to characterize dynamic and complex intercellular interactions that occur during progressive injury. Here we discuss the utility of 3D bioprinted liver for studying chronic exposure using fibrosis as a case study and provide a comprehensive approach to examine key initiating events and progression of tissue injury.