EUREKA PROJECT > 2674 MIDAS
UNITED KINGDOM
MEDICAL DIAGNOSTICS APPLIED TO SURGERY
THE AIM OF THE PROJECT IS TO DEMONSTRATE THE FEASIBILITY OF A NEW DIAGNOSTIC TEST THAT SIGNIFICANTLY REDUCES THE RISK OF SHORT-TERM REJECTION IN TRANSPLANT SURGERY.
Status > FINISHED - 23-Mar-2004 Technological Area Market Area Start Date > 01-Nov-2001 Duration > 24 Months Participating countries > UNITED KINGDOM, GERMANY | Main contactPROIMMUNE LIMITED
DR. NIKOLAI SCHWABE > CHAIRMAN AND CHIEF EXECUTIVE OFFICER Organisation type > SME |
Project Description
Organ transplantation involves the surgical replacement of the failed organ of a transplant recipient with a viable organ from a donor. Transplantation has become increasingly important in recent years as a means to overcome acute and chronic organ failure due to improvements in the supply logistics for donor organs and improved surgical techniques leading to longer graft survival rates. Transplantation remains a significant challenge today due to the limited availability of donor organs that match the so-called 'tissue type' of the recipient, i.e. that are compatible with the recipient. Difference in the tissue type between donor and recipient of a transplant cause rejection of the donor organ by the recipient's immune system. If this rejection reaction is not treated through the administration of drugs that suppress the immune system, the donor organ is normally destroyed within a short period of time. In order to minimise the need for immuno-suppressive drugs following transplantation it is desirable to select a donor organ that matches the tissue type of the recipient as closely as possible. Today this is normally achieved by making a genetic comparison of the donor and the recipient tissue. However, the mere genetic difference between the transplant donor and recipient only plays a partial role in the likelihood of rejection. The other very important factor is the previous environmental exposure of the recipient. Due to, for example, prior transplantations, pregnancies, and blood transfusions a patient may be particularly sensitised to certain determinants of foreign tissue types. As a consequence a patient who is reasonably well matched to a donor organ may mount an unexpected acute rejection of the donor organ, which negates the effort of transplantation often within hours of surgery and presets a significant risk to the patient's life. The project proposes to develop a new diagnostic test, based on recombinant DNA technologies that significantly reduces the risk of short term rejection in transplant surgery. To this end the project will make use of previous developments at PROIMMUNE funded by DTI Smart award. The testing format envisaged will be cheaper and easier to use than existing testing methods. Designing and evaluating the proposed diagnostic test requires access to data and serum samples of transplant patients. For this reason PROIMMUNE will collaborate with the clinical transplant immunology group of Dr. Westphal at the UNIVERSITY OF KIEL in this project. Keywords: medical diagnostics, transplant surgery, biotechnology.
Technological Development Envisaged
The technical part of the project will deliver a range of recombinant protein molecules to be used in testing as well as a validated physical testing format. Starting from a simple group of base-molecules the test will evolve throughout the course of the project in several iterations. Specifically, the test under development will be used with existing patient sera to obtain comprehensive, statistically significant clinical data on test effectiveness. At the same time the sera will be tested with current standard methods to compare results. Data obtained will be used to determine the specificity and reactivity of the new test format in comparison and to validate the technical principle of the test. These data will play an important part in optimising the reagent composition of the test.
Main contactPROIMMUNE LIMITED
DR. NIKOLAI SCHWABE > CHAIRMAN AND CHIEF EXECUTIVE OFFICER Organisation type > SME |
Contribution to project
In order to promote experimental use of the diagnostic test to be developed, PROIMMUNE will develop new contacts with further transplant centres in the UK, the US and Asia.
Expertise
Expertise: new biotechnology venture setting out to deliver value-added solutions for medical research, diagnosis and therapy. The company was founded by Dr. Linda Tan and Dr. Nikolai Schwabe in November 1999 and commenced operations in February 2000 at the Oxford BioBusiness Centre, an incubator site for biotechnology companies. The company's central focus is molecular immunology. PROIMMUNE has developed substantial proprietary know how in this area in a one-year development project funded by a DTI Smart award. The company currently employs a team of four PhDs and is actively recruiting to expand its manufacturing and research efforts. Techniques required for carrying out PROIMMUNE's part of the project include protein design, molecular biology and cloning techniques, such as PCR and site directed mutagenesis, design and use of recombinant expression systems, such as bacterial and insect cell culture using various vectors and cell lines, protein expression, manipulation, purification and analysis, such as western blotting, polyacrylamide gel electrophoresis and high performance liquid chromatography HPLC. Contribution: An initial test format will be designed based on a small number of relevant molecules that are currently available at PROIMMUNE. An initial test format will be developed by immobilising molecules on a solid support that will evolve throughout the project. Over the course of the project PROIPMMUNE will develop a wider range of recombinant protein molecules to be used in testing. The choice of molecules to be developed will be based on clinical data made available from Dr. Westphal's group throughout the project. In addition, PROIMMUNE will evaluate business development partnerships with companies that are already established in the medical diagnostic area. It is envisaged that under such a partnership they would still carry out all of the manufacturing of the final test while the partner organisation would mainly be responsible for distribution and direct contact with clinicians.
Main contactUNIVERSITAETSKLINIKUM KIEL/INSTITUT FUER IMMUNOLOGIE
DR. ECKHARD WESTPHAL > LECTURER Organisation type > University |
Contribution to project
The objective of the involvement of Dr Westphal's group in this project is to carry out clinical testing and interpret testing results from a clinical point of view.
Expertise
Expertise: The group of Dr Eckhard Westphal at the Institute for Immunology of KIEL's UNIVERSITY HOSPITAL has been involved with the testing and matching of donors and recipients in transplantation for many years. As an accredited laboratory within the EUROTRANSPLANT consortium, Dr Westphal's group is responsible for testing substantially all sera to be evaluated for renal transplantation within northern GERMANY. As a consequence of its long-term involvement in the area, the group has direct on-site access to several thousand current and historical patient sera. In addition, the group has in-depth experience with carrying out current standard compatibility testing methods, which require a high level of manual skill and pertinent expertise. Furthermore, Dr. Westphal's group has substantial expertise in interpreting test data and determining the effectiveness of testing methods by comparing patient outcomes with testing results. Contribution: This expertise will enable PROIMMUNE to design the diagnostic test and choose its composition to make its relevance and ease of use for the clinical investigator. Specifically, Dr Westphal's group will use the test format as it evolves throughout the project to test serum samples from transplant recipients taken prior to transplantation, for which the outcome of transplantation is already known. This will enable PROIMMUNE to establish which molecular determinants are most relevant. Serum samples will be supplied by Dr Westphal's group. The results obtained will be compared with genetic tissue typing data from patients and organ donors and with results obtained from parallel testing with standard methods in current clinical practice. In addition the interpretation of testing results will be an important contribution in determining crucial parameters for the final testing format, which will be an essential step in validating the test format and composition chosen.