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Drug Discovery Protein Profling "Our team was the frst to conduct an indepth molecular comparison of cancer and normal tissues for the presence of cancer stem cells," says David. M Lubman, Ph.D., professor of surgery at the University of Michigan, Ann Arbor. "Our method overcomes a common problem of heterogeneity of cancer tissues. Most surgically removed tissue samples contain a low percentage of tumor cells embedded in a dense stroma. Identifcation of crucial cancer biomarkers requires analysis of a pure and homogeneous cell population." "However, usefulness of microdissection is often limited by the diffculties in identifying desired cell types by morphology alone." Dr. Lubman's team used a combination of immunostaining with laser capture microdissection (immuno-LCM). "This method allowed us to zero in on a small population of cancer stem cells expressing CD24, a specifc cell surface biomarker shown to correlate with the development and metastasis of pancreatic cancer," continues Dr. Lubman. "The excised material contained only 10,000–15,000 cells." Analysis of immunophenotypically defned cell populations markedly increased specifcity of liquid chromatography-tandem mass spectroscopy (LC-MS/MS). Over 375 differentially expressed proteins were analyzed by Ingenuity Pathway Analysis (Ingenuity Systems). Not surprisingly, the major groups of differentially expressed proteins were involved in tumor migration, invasion, Continued from page 1 and progression. Three selected candidate biomarkers (CD59, CD70, and CD74) mediate the evasion of the immune response. Overexpression detected by MS was further confrmed by tissue staining and microarrays. CD74 specifcally correlated with early cancer development and was critically positioned in the NFκB signaling pathway. "The early appearance of CD74 means that this candidate biomarker could be a promising tool in therapeutic drug discovery. Our next step is to search for these biomarkers in serum," asserts Dr. Lubman. Improved Sensitivity of MS Analysis According to Yuri van der Burgt, Ph.D., at the Leiden University Medical Center in the Netherlands, sample workup is an essential part of any proteomics workfow. "Biomarker discovery requires both reSee Protein Profiling on page 21 Early cancer biomarkers identified from homogeneous cell populations procured from frozen tissues using i-LCM and LC-MS/MS. Lubman Research Lab, University of MIchigan The Sweedler laboratory at the University of Illinois at UrbanaChampaign uses a unique approach for collecting neuropeptides from a living brain slice for mass spectrometry characterization. NEWS Discovery & Development > MultiCell, Genisphere to Target Liver Cancer with Nanoparticles MultiCell Technologies and Genisphere are working together to develop a targeted MCT-485 nanoparticle therapeutic for the treatment of liver cancer. MCT-485 is a noncoding, doublestranded microRNA (miRNA) which has reportedly demonstrated oncolytic and immune-stimulating activity in in vitro models of hepatocellular carcinoma. The two frms will investigate the use of Genisphere's 3DNA® Dendrimer nanoparticle drug delivery technology to enable the targeted delivery of MCT-485 to the tumor and away from normal tissues. Formulations that meet several criteria, including being safe enough to allow parenteral administration by infusion or topical administration, will be developed and tested in animal models of hepatocellular carcinoma. MCT-485 possesses both oncolytic and immune activating properties, which, according to MultiCell, means it could provide a more robust activation of immunity and a more global and longer- 18 | lasting antitumor efect than currently marketed chemotherapies. > Athersys Gets Up to $2.8M for for infammatory bowel disease and with RTI Biologics in September of 2010 to develop a bone allograft product in the orthopedic market. royalties on global net sales of any resulting products under the collaboration. > Bayer Partnership Could Ensemble Therapeutics launched a pair of R&D; collaborations with Novartis based on the pharma giant's licensing of the biotech's class of IL-17 antagonists. One collaboration is based on antagonists of the infammatory cytokine implicated in multiple infammatory and autoimmune diseases. The other will apply Ensemble's drug discovery platforms to discover new small molecule treatments against undisclosed Novartis-specifed drug targets. Under their global strategic collaboration, Ensemble will receive an undisclosed up-front payment from Novartis, and will be eligible for potential payments tied to development and sales milestones. Ensemble will also receive research funding from Novartis, as well as tiered royalties on potential future sales of products that may result from the collaboration. Heart Attack Regen Med Program Athersys received an SBIR fast-track grant from the National Heart, Lung, and Blood Institute to support a Phase II clinical study evaluating the administration of Athersys' MultiStem® therapy to patients who have sufered a heart attack, also known as acute myocardial infarction (AMI). The grant is expected to provide up to $2.8 million in support over the course of the study in connection with study progress and milestone achievement. MultiStem cell therapy is a regenerative medicine product that, according to Athersys, can promote tissue repair and healing in diferent ways. In addition to cardiovascular disease, MultiStem has reportedly demonstrated therapeutic potential for the treatment of infammatory and immune disorders, neurological conditions, and other illnesses. Athersys entered partnerships with Pfzer back in December of 2009 to develop MultiStem September 1, 2013 | GENengnews.com | Genetic Engineering & Biotechnology News Net $540M+ for Compugen Bayer HealthCare will team up with Compugen on preclinical research toward antibody-based cancer immunotherapies against two potential immune checkpoint targets discovered by Compugen, with Bayer exercising full control over further development and holding worldwide commercialization rights for any resulting cancer therapeutics. The deal could generate more than $540 million for Compugen. Under a collaboration and license agreement, Bayer agreed to pay Compugen $10 million up front, with up to $30 million in payments tied to preclinical milestones. Compugen is also eligible to receive over $500 million in potential payments tied to additional undisclosed milestones for both programs. The company may also receive mid- to high-single-digit > Novartis, Ensemble Therapeutics Launch Collaborations See News on page 21