End-stage kidney disease is the last stage of a chronic kidney disease, which if not addressed leads to premature death and, although it can be addressed by dialysis, kidney transplantation is the preferred treatment due to better survival rates, improved quality of life & cost efficiency. The most important challenge is to achieve the long-term survival of the transplanted organ. Graft survival depends on the ability of the recipient of not rejecting the foreign organ. Rejection is a naturally occurring process triggered by a biological response of the immune system and nowadays it is prevented by immunosuppressive therapies. Although these therapies have represented a huge step forward in organ transplantation, their use still entails important problems:
Suppressing the immune system implies severe side effects like infections, cancer and other severe pathologies.
Even under immunosuppressive therapies, about 50% of transplanted kidneys are lost during the first 10 years and there are several reasons but the most important is related to rejection mechanisms.
Therefore, the major challenges in kidney transplantation deal with avoiding the side effects associated with immunosuppressant drugs and avoiding rejection. In TRANSBIO we aim at bringing to the market a non-invasive blood test that will provide an important piece of information to personalize and monitor the adequacy of immunosuppressive therapy for each patient.
The IVD test has been named Inmunobiogram®. It is a combination of a biotechnological assay and software for data analysis. Specifically, to run the bioassay a 10mL sample of blood from the patient is needed. It is set up a PBMCs 3D culture in semi-solid matrix submitted to specific stimulation which replicates antigen presentation. Inmunobiogram® mimics immune response in which PBMC replicate and expand (C+), and this response is compared with no stimulation (C-) and with stimulation in presence of immunosuppressants (C+ with IMs). Data is analyzed with a software and output is an evaluation of the sensitivity degree of patient´s circulating immune cells to a panel of immunosuppressant most recommended in clinical guidelines and most used in the clinical setting. The bioassay uses well known immunosuppressants, but it can be adapted for testing new compounds against marketed ones.
Considering that worldwide, the number of people receiving renal transplantation annually is estimated at about 80000 people, growing by approx 6% annually and representing a prevalence of about 700 patients per million population, or what is the same about 5 million people living with a transplanted kidney.
In this project, performed in collaboration with renowned international experts in Nephrology, our goal was to evaluate the analytical robustness and clinical utility of our technology through clinical program comprising two studies. This will enable us to get the regulatory approval (CE marking) for commercialization and bring our product to the healthcare market. The specific objectives are as follows:
1. To optimize the prototype test kit. A price reduction of 25-30% can be achieved by reducing the number of cellular/molecular markers involved, to those most relevant. This prototype optimization was to be done by a pilot clinical study
2. To perform a multicenter validation study in collaboration with some of the most relevant Nephrology Transplantation Units in EU. This clinical study will be aimed at validating the actual analytical robustness of the test and correlation with clinical outcomes, for its approval by the regulatory bodies.
3. To develop a bioinformatics platform as a software tool, based on the results of the clinical validation study. The software will analyze the test results and will deliver the report with the conclusions of the test.
