Three-way triple threat

Vivo Biosciences, ACEA Biosciences and Roche to develop xCELLigence System assays for stem cell and cancer research

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PENZBERG, Germany—ACEA Biosciences Inc. and Vivo Biosciences Inc. have agreed to work together to further develop label-free and real-time cell-based assays for the xCELLigence System, which is co-developed by Roche and ACEA and marketed by Roche Applied Science. Financial terms of the collaboration have not been released.

"The new HuBiogel-based assays will further increase the application field for the xCELLigence System, in low and high-throughput formats," says James P. O'Connell, CEO of ACEA Biosciences.

The new assays will incorporate Vivo's proprietary platform HuBiogel, a human-derived, natural, biomatrix system that allows for growth, proliferation and differentiation of primary cells, cancer cells and stem cells in a 3D format and physiologically relevant environment that closely mimics the in vivo environment.

According to Raj Singh, president and CEO of Vivo, HuBiogel provides physiologic-relevance though its human biomatrix composition and in vivo-like microenvironment. Additionally, HuBiogel allows "all-human" assay systems for studying the biology of normal (liver) and disease (tumor) tissues in parallel. Singh points out that it overcomes many limitations of current synthetic and animal-based matrix models.

"Vivo has developed a series of 3D human bioassay systems using NCI-panel and patient-derived tumor cells," he adds. "In replicating tumor microenvironment or heterogeneity, they will advance oncology research by offering better real-time functional, preclinical and prognostic endpoints."

Singh notes that this is the first research and development collaboration between the companies. However, ACEA Biosciences and Roche Applied Science have been marketing and development partners for the past three years.

Singh explains that Vivo's primary objective is "to integrate high-value HuBiogel culture technology for new real-time oncology assay applications, e.g., tumor growth, angiogenesis, invasion and EMT."

In addition to the oncology collaboration, Singh says the partnership will jointly explore other real-time bioassays with utility of stem cells, hepotocytes and other primary cells.

"By combining this unique biology model, our R&D collaboration shall benefit various markets of Acea-Roche xCELLigence System," he says.

The xCELLigence system encompasses a series of RTCA instruments that utilize specially fabricated microplates containing microelectrodes for real-time dynamic monitoring of cell behavior under label-free conditions. A number of cell-based applications, including cell proliferation and cytotoxicity, cell adhesion, cell migration, and invasion and receptor-mediated signaling have been developed on the xCELLigence Platform.

"Roche Applied Science believes that the combination of its unique cell invasion monitoring technology with a human biomatrix can significantly support and accelerate oncology research in analyzing the invasive potential of tumor cells," notes Ruedi Stoffel, Life Cycle leader for Cellular Analysis at Roche Diagnostics.

Dr. Burkhard Ziebolz, head of global communication for Roche Diagnostics, points out that Roche Applied Science has launched a product portfolio, allowing the analysis of cell migration and invasion (CIM) in real-time, as it occurs.

"The system consists of the xCELLIgence RTCA DP System for impedance-based analysis of multiple cellular phenomena," he explains. "A special disposable device, the CIM Plate 16, allows combined real-time acquisition of impedance readings with a Boyden-Chamber-type approach to measure CIM with no labels, and in real time."

According to Zeibolz, the device alone is capable of supporting analysis of cell migration; however cell invasion as it occurs during tumor spreading (according to common understanding) requires a cell's capability to degrade and invade into extracellular matrix (ECM) material.

"Researchers therefore need to add such matrix material to the CIM plates prior to the experiment," he says. "Roche is interested in providing customers with best-suited protocols and materials for that purpose."

According to Ziebolz, Roche's mission is providing state-of-the-art solutions for life science research.

"As such, the potential of combining Roche's RTCA CIM Plate with the only commercially available extra-cellular matrix material of human origin represents another step in improving researchers' capability for developing truly relevant in vitro test systems," he says.

Moreover, the collaboration could ultimately have a positive impact on Roche's pipeline, he adds.

"Roche Applied Science's CIM System, in combination with a human ECM, will allow researchers derive more relevant data from the experimental studies, thus strengthening RAS' overall position in the market with CIM," Ziebolz says.

The collaboration also can have wide-ranging impact on oncology research. Ziebolz points out that oncology researchers are constantly looking for in vitro model systems that can recapitulate and truly capture the tumor microenvironment for both mechanistic understanding of the tumor, and for drug screening and drug development.

"The human-derived bio-relevant matrix from Vivo, coupled with the non-invasive nature of the xCELLigence readout, has the capacity to accomplish this goal in several ways," he says. "The non-invasive kinetic readout of the xCELLigence system allows for functional and mechanistic assessment of tumors over time, and at the same time provides a more comprehensive representation of how the tumors growing in a biologically relevant microenvironment respond to anti-cancer drugs. Furthermore, since Vivo's Hu-Biogel also supports angiogenesis—a common feature of most if not all tumors—the xCELLigence system can be used for the screening of anti-anigiogenic peptides and compounds as well." 

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