Immunomedics Announces Preclinical Results of Milatuzumab in B-Cell Malignancies

Immunomedics, Inc. at the 51st annual meeting of the American Society of Hematology announced results from 3 preclinical studies aimed at understanding the mechanism of action of its proprietary humanized anti-CD74 antibody, milatuzumab, which is currently in clinical development for multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL).

The first study was on CLL, a progressive disease for which most patients require treatment. A team of researchers at the Ohio State University, Columbus, OH, led by Dr. John Byrd, demonstrated expression of CD74 on the surface of CLL cells, but no expression was found on T cells. Milatuzumab-induced cell death occurred very rapidly, with 57% cell survival at 4 hours and only 30% at 24 hours, which was superior to that observed with rituximab.

The mode of cell death induced by milatuzumab was found to be mediated directly through interaction with CD74 and its ensuing effects on signal transduction. Milatuzumab, when crosslinked, promotes the maintenance of CD74 on the cell surface and thereby prevents receptor internalization and subsequent signaling. Retention of the CD74 receptor on the surface of B cells can also be induced, without the presence of a crosslinking antibody, the investigators found, by incorporating milatuzumab into liposomes. The subject of the second study was mantle cell lymphoma (MCL), an incurable B-cell malignancy with limited therapeutic options. Despite the success of rituximab in treating B-cell lymphoma, its use as a single agent or in combination with chemotherapy in MCL has demonstrated modest activity. Since rituximab and milatuzumab target distinct antigens lacking known association, Dr. Byrd and his team at the Ohio State University, explored a combination strategy with these antibodies in MCL cell lines, patient samples, and in a preclinical model.

U-Iowa study helps advance heart-related research (PLoS)

Using a new mathematical model of heart cells, University of Iowa investigators have shown how activation of a critical enzyme, calmodulin kinase II (CaM kinase), disrupts the electrical activity of heart cells. The study, which also involved Columbia University, was published online Dec. 3 in the journal PLoS Computational Biology.

"Recently, researchers have developed great interest in calmodulin kinase II as a critical regulator of the heart's response to injury. By targeting this enzyme's activity, it may be possible to prevent or treat heart disease and associated electrical rhythm disturbances," said Thomas Hund, Ph.D., associate in internal medicine at the University of Iowa Roy J. and Lucille A. Carver College of Medicine and the paper's senior author.

"CaM kinase is activated when the heart experiences injury, for example, when an artery providing blood to the heart becomes blocked. In the short-term, this increase in activity may be the heart's attempt to increase blood flow," Hund said. "However, unfortunately, the initial response results in a vicious cycle that likely advances heart disease."

In this study, the team analyzed tissue from injured hearts from animals, in which a coronary artery had been blocked. They found a dramatic increase in the levels of oxidized CaM kinase in specific heart regions where potentially lethal electrical activity occurs. Using the mathematical model of the cardiac cell, the researchers were able to predict, through computer simulation, the effects of oxidized CaM kinase on cardiac electrical activity. Oxidation activates the enzyme by modifying key chemical groups. In heart disease, oxidation is overactive, and CaM kinase is turned on too much. Visit the PLoS portal to review the full research abstract

Fluidigm Releases Access Array™ System for 454 FLX Applicon Tagging

Fluidigm released its 48.48 Access Array™ integrated fluidic chip (IFC) for 454 FLX™ users active in Amplicon Tagging. This Access Array IFC automatically generates emPCR-ready libraries by simultaneously combining 48 samples and 48 primer sets to produce 48 uniquely-barcoded samples per chip for approximately $7 (U.S.) per sample.

Fluidigm’s Access Array IFC, when used with a 454 FLX sequencer, can capture up to 12 kb of sequence data per sample, or 576 kb per array. Upcoming applications on the Access Array system, such as long range PCR, will allow for users to target up to 480 kb of sequence data per sample, or 23MB per array.

“Fluidigm’s Access Array System has already been adopted by users around the world for targeted re-sequencing projects focused on research of cancer, miRNA, and population genetics, where the ability to inexpensively sequence large cohort studies is critical,” noted Mike Lee, Fluidigm’s Senior Director of Marketing. “The flexibility, ease of use, and cost effectiveness of our Access Array system will enable researchers to expand the scope of experiments on next generation sequencers,” he added.

Sequencing library preparation for next-generation sequencers is by far the most time and labor demanding component of the entire next-generation sequencing process. While necessary for whole genome sequencing studies, the process can be almost entirely eliminated for targeted re-sequencing projects through the use of amplicon tagging. By incorporating the adaptor sequences into the primer design, the final PCR product is ready to go into emPCR or onto the flowcell since it already contains the necessary capture sequences. The Fluidigm product portal has complete techncail and performance details

PerkinElmer Launches New AlphaScreen® SureFire® and AlphaLISA® “No Wash” Immunoassay and Cellular Pathway Mapping Kits

PerkinElmer announced the expansion of its “No Wash” ALPHA (Amplified Luminescent Proximity Homogeneous Assay) Technology portfolio by introducing 46 new highly sensitive cell signaling pathway and biomarker research assay kits. The new assays provide researchers with comprehensive tools for advancing studies in cancer, inflammatory, and neurodegenerative disorders.

PerkinElmer’s AlphaScreen®SureFire® assays enable researchers to save time by providing the ability to study key biological pathways using the same sample and conditions in a single experiment. In addition, the kits simplify complex protocols, increasing the ability to automate high-throughput screening processes and assisting researchers in the transition from time-consuming Western Blot or ELISA methods.

In addition, the Company’s AlphaLISA® “No Wash” immunoassay kits enable the study of biomarkers for multiple disease states. The latest assays include human and mouse biomarker targets, significantly broadening the applicability of the ELISA-alternative ALPHA technology portfolio.

“PerkinElmer continues to make great strides with the expansion of the ALPHA Technology portfolio, based on scientific demand for alternative ways to measure cell signaling pathways and biomarkers,” said Richard M. Eglen, PhD, president, Bio-discovery, PerkinElmer. “The new kits will help open new directions in research for diseases such as cancer, Alzheimer’s, cardiovascular and inflammatory conditions.” Th PE product portal provides comlpete techncial and performance details

Applied Biosystems Debuts Industry’s First Acoustic Flow Cytometer

Applied Biosystems, part of Life Technologies Corporation announced its entry into the flow cytometry instrumentation market with the debut of the Attune™ Acoustic Focusing Cytometer, a first of its kind cytometry system designed to use sound waves to precisely control the movement of cells. The company has built upon its expertise in instrumentation, as well as its position as a long-time leading provider of flow cytometry reagents, to create a technology that will offer customers enhanced sample throughput, sensitivity and accuracy for a range of cell biology applications.

Flow cytometry allows scientists to count and examine cells by passing them through a laser-based detection device. Thousands of cells per second may be counted, allowing rapid characterization of entire populations of cells. Cellular biologists engage in flow cytometry for a rapidly growing range of applications, including the study of proteins expressed by cells (immunophenotyping), quantifying the amount of DNA in cells, cell counting, among others.

Attune enables scientists to gather statistical data on a large number of heterogeneous cells to study parameters within a cell population, including size, complexity, phenotype and health. Attune’s proprietary technology allows scientists to achieve enhanced sensitivity, saves time by increasing throughput, and can be used with small sample sizes. In addition, it offers these enhanced capabilities with a reduced footprint due to the compact acoustic technology and the far smaller volume of consumables required to perform an experiment. These unique capabilities will enable scientific applications not previously possible on traditional cytometry systems, ranging from sample preparation to bead-based analyses. Visit Life Technologies' press room for complete solution details