Meeting the Challenge of Treating Diseases with High Unmet Medical Need

October 20, 2014

High content imaging analysis of drug-resistant bacterial cells.

AIMM Therapeutics is a privately held research-based biotechnology company located in Amsterdam. Their research programs target the prevention and treatment of diseases with a high unmet medical need, including cancer, inflammatory diseases, autoimmune diseases and infectious diseases.

A Desperate Need for New Treatments for Drug-resistant Bacterial Infections

Infection with the intestinal bacterium Clostridium difficile (C. difficile) is the most common cause of healthcare-associated diarrhea. It can develop in patients after hospitalization and treatment with antibiotics. Symptoms of C. difficile infection (CDI) vary from mild diarrhea to full-blown clinical expression with severe inflammation of the colon (pseudomembranous colitis or PMC), which can result in colonic perforation, septicemia and death. C. difficile is resistant to a wide range of antibiotics, so for this reason new treatments for severe cases are desperately needed.

The Fight Against C. difficile

CDI is mediated by the production of toxins by the bacterium, with toxin A (ToxA) and toxin B (ToxB) responsible for the most common symptoms seen in the clinic. Because of this, treatment with toxin-binding agents such as antibodies is a promising approach to reduce or inhibit PMC. The first step in the process of generating antibodies is the isolation of memory B cells from blood samples. However, these B cells are not suited for long-term use and so first need to be adapted.

AIMM uses its proprietary technology called AIMSelect™ platform to transform peripheral blood memory cells from exposed individuals into immortalized cells, using genetic programming. These immortalized cells will not undergo spontaneous differentiation into other cell types.

"Before we used the Operetta® system, we analyzed plates with a conventional microscope, which resulted in the researcher getting many headaches! Now, the Operetta system allows us to automate imaging and to achieve higher speed and throughput."

- Dr. Mark Kwakkenbos, Scientist, AIMM Therapeutics, Amsterdam

Developing Therapeutic Antibodies

To identify B cell clones that secrete ToxA and ToxB specific antibodies, ELISA assays are first performed on the EnVision® Multilabel Plate Reader.

Scientists also need to test which antibodies are the most effective, i.e. offer the highest protection against the toxic effects of C. difficile ToxA and ToxB. To do this, functional antibody characterization studies are performed using the Operetta® High Content Imaging System.

The Operetta system is coupled to a plate::handler workstation and the Columbus™ Image Data Storage and Analysis System. The images that are acquired using the Operetta system are transferred to the Columbus system for analysis. Incubation of cells with the toxin leads to cell rounding; therefore the toxicity of toxin/antibody mixtures can be determined in Columbus by scoring the roundness of cells.

Using this proprietary, state-of-the-art antibody technology platform, AIMM is able to develop therapeutic and prophylactic human monoclonal antibodies from immortalized and selected B cells.

Enabling Much Needed Treatments, Sooner

AIMM has been able to establish a workflow using PerkinElmer's High Content Imaging solutions that greatly reduces the amount of work, time, testing and reagents needed to support the development of therapeutic antibodies. These rapid development timelines result in earlier availability of much-needed therapeutics that could significantly improve the treatment of CDI, as well as other diseases with high unmet medical need.

For Research use only. Not for use in diagnostic procedures.


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