Biosensor Used to Help Anticancer Resistance

A powerful new biosensor developed by European researchers should help to identify cells in the immune system that actively inhibit tumor growth, and then put them to use.

Cancer is a major killer and a difficult problem confronting the medical community, but now this new technology help doctors to use the patient's own immune system to fight the disease. Moreover, during their work, the team of researchers, from MindSeeds Laboratories (Bologna, Italy), discovered that the breakthrough technology could be used in a variety of other applications, from biotech, to green tech, to industrial processes. The biosensor for cancer therapy, however, was the primary focus of the group.

Currently, many cancer therapies in the domain of immunooncology use immune system enhancing drugs such as interferon, interleukin 2, or various types of colony-stimulating factors (CSFs), which, unfortunately, can cause a reaction. A better approach would be to select the "active cells,” which are successfully fighting the cancer cells, amplify them in a test tube, and then reinject them into the body. Here, doctors would only be assisting the patient's own immune system to fight the tumor, with no risk of rejection or side effects.

But there is a problem. With current technology, there is no easy, cost effective, and effective way to identify the active cells. That has changed thanks to the work of the Cochise (Cell-On-Chip biosensor for detection of cell-to-cell interactions) Project. The Cochise team developed a biosensor capable of identifying interactions between single cells. A biosensor is simply an instrument designed to detect signals from biological activity.

The Cochise biosensor uses a combination of microfluidics and electronics to first isolate immune system cells and cancer cells in a microwell, and then identify the active cells. Key to this analysis are the electronics, firstly the dielectrophoresis, which forces the cells together so doctors, can observe interactions between them. Active cells are then separated from the rest.

"The procedure we identified for measuring cell activity is at the core of the technology,” said Massimo Bocchi, CTO at MindSeeds Laboratories, a researcher on the project. Basically, we demonstrated, using reference cell lines, that the expected interactions between cells of the immune system and tumor cells can be reproduced in microstructures, such as the microwell, at the single-cell level. When an event of interest is measured... [say] a cell of the immune system kills a target tumor cell; the cell of interest can be retrieved from the platform, transferred to a standard plate, and cultured. This complete workflow allows doctors to study the behavior of cells because we are able to isolate them on the basis of their functional activity. This is a key innovative concept in this field.”

The group achieved their goal, and accomplished a host of research successes along the way, particularly the development of a new fabrication process and finding appropriate biocompatible materials. "This was carried out during the project, demonstrating the possibility to fabricate disposable devices with a production technology which can be industrialized, thus supporting large-volume production,” Mr. Bocchi stressed.

It is an impressive result, because the biosensor's usefulness goes way beyond identifying active cells. The technology could introduce new methods for producing targeted cancer vaccines, introducing a sort of "tuning of the patient's immune system,” suggested Mr. Bocchi.

Another hurdle in therapeutic protocols today is the difficulty in determining the effect of a therapy on the tumor. Frequently feedback comes too late, when additional therapeutic steps cannot be undertaken. This technology has the potential to improve therapeutic protocols, due to prior monitoring of the patients' responses.

The prototype works, delivering live, active cells from the biosensor for amplification, but there is more work required before it is ready for commercialization, and the partners are looking to develop a larger European integrated project to achieve that.

The biosensor works well, but evaluating one cell at a time for "useful interactions” is too slow--because the Cochise project expects that in any sample there will be very few cells that interact helpfully and medical labs need to be able to test thousands of cells at a time. "This level of parallelism is a key issue, we need to explore up to 10,000 interactions before finding an interesting one,” Mr. Bocchi revealed. Additional development is necessary to reach that sort of processing capacity in parallel. For this reason, Mr. Bocchi believes it could be three to five years before this biosensor reaches medical labs.

But the project is already generating a lot of interest from industry and peers. "Several research institutes and hospitals [showed interest] in this platform for studying the mechanisms of the immune system with a single-cell resolution, and to see the potential applicability to gene-therapy applications. Many pharmaceutical companies, instead, see a potential application in the field of industrial biotechnology and have [shown] interest in using this technology to improve some critical steps commonly found, for instance, in the production of monoclonal antibodies,” noted Mr. Bocchi.

A start-up company, Mindseeds Laboratories, was founded with the aim of commercializing the work, but that will take time and further research. Cochise has demonstrated, however, that biosensors have an important role to play in the development of novel therapeutic paradigms, where the patients do the healing.

Mindseeds Labs joined the European Union (EU)-supported COCHISE project for the development of a biosensor for the detection of cell-to-cell interactions. COCHISE is a three-year research project starting on June 1, 2006, aiming at developing a technology, which finds applications in cancer therapy and monitoring.

Mindseeds Labs plans to exploit the entire technology, consisting of biosensor architecture, system, and screening protocols, in the area of oncology.

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MindSeeds Laboratories