Pictures of the Future      Fall 2008

New Hope for Organ Transplants

A blood test developed by Cylex Inc. can help determine how well a patient’s immune system is functioning. Siemens Venture Capital has invested in the company.

Following a transplant, there is always a risk that the recipient’s immune system might reject the donor organ. Although progress has been in this area with medications, the latter also reduce the body’s ability to combat pathogens. Doctors must thus give patients just enough medication to ensure that the new organ won’t be rejected while retaining enough of the body’s resistance to viruses and bacteria. Doing so is complicated because so far it hasn’t been possible to determine the state of a patient’s immune system. Although simply counting the number of T-lymphocytes (white blood cells that support an immune response) in a blood sample has often been used, this approach doesn’t reveal how actively the cells can combat pathogens. In fact, 100 very active lymphocytes might function more effectively than 1,000 sluggish ones.

To address this problem, Cylex Inc. in Columbia, Maryland, developed the world’s first FDA-cleared clinical diagnostic test to determine how well a patient’s cellular immune system functions. Cylex’s current assay, ImmuKnow, involves adding phytohemagglutinin (pha), a lectin extract from red beans, to a blood sample. In a complex series of biochemical reactions, this substance acts as an immune stimulant (like viruses or bacteria) resulting in the activation of the cells and the increased production of adenosine triphosphate (ATP) in T-lymphocytes. ATP transports energy for many body processes and can thus help measure T-lymphocytel activity. After an incubation period of up to 18 hours, tiny magnetic spheres coated with antibodies are added to the blood. On the T-lymphocytes is a CD 4 receptor molecule, which docks with the antibodies. The T-lymphocytes that are enriched with ATP can now be extracted from the blood sample with the help of a magnetic field. The ATP inside the cell is then released and mixed with luciferin (a substrate) and luceriferase (an enzyme), generating a luminescent reaction. This reaction emits light, with the intensity depending on the concentration of ATP in the solution. This means that the more ATP a sample contains, the brighter it will shine, enabling the assay to measure the activation of T-lymphocytes and doctors to gauge the immune system’s activity.

"Our ability to tell how well the immune system is functioning is revolutionary," says Brad L. Stewart, President of Cylex. "It’s also novel to cause the reaction to take place in a whole blood sample so that the processes occurs as if in a patient’s body. In addition to focusing on making the procedure cheaper and faster, we have two other development aims," says Stewart. "For one thing, we have so far primarily focused on  immune cells with CD 4 receptors, but there are also cells that have many other types of receptors, such as B-lymphocytes, that are part of the body’s adaptive immune system. Additionally, the functionality of the immune system is critical for many areas outside of transplant medicine such as HIV, hepatitis C, cancer, and autoimmune disorders,"  he says. The total market for the technology is around $1.8 billion.

Siemens Venture Capital (SVC) invested in Cylex in March 2007, because of the company’s interest in diagnostics and its unique concept of cell-mediated immunity. "We are committed to personalized medicine in which treatment is tailored to the patient," says Anupendra Sharma, Investment Partner at SVC, and an Observer on the Cylex Board of Directors. "To achieve this goal we will need products that make it possible to test the effectiveness of medication that suppresses the immune system. Cylex’ technology ideally supplements our own developments." Sharma points to many ways in which Siemens Healthcare could work with Cylex, ranging from the development of automated processes to providing support for the international marketing of its product.

After its success in the U.S.—over 125 transplant centers are using the assay—Cylex has now expanded into Europe and Asia. In Germany, the ImmuKnow assay is being used by labs at the universities in Göttingen and Bochum. The test has also been introduced at key labs in Italy and Spain. Its prospects are extremely good, since it helps provide better healthcare. For example, morbidity in organ transplantation is severe and post-transplant expected life span is only two to five years. A tool such as ImmuKnow, which helps physicians more effectively manage these patients, is a welcome and valuable addition.
                                                                                                                Bernhard Gerl