BIOHOPE is developing a blood-based in vitro diagnosis test to personalize immunosuppressant therapy for renal transplanted patients under treatment with immunosuppressant drugs. This diagnostic kit been named Immunobiogram® (IMBG) – Transplant.

 

Inmunobiogram® is being studied in Renal Transplantation under a comprehensive clinical plan program, which includes a first proof of concept clinical study in 70 patients (BH-Pilot) and an international validation study in 200 patients (TRANSBIO clinical study)

“BH-Pilot” was a clinical study performed in 2017 in “La Paz” and “Puerta de Hierro” University Hospitals (Madrid). An interim analysis showing a positive proof of concept was presented at an investigator meeting with our Scientific Advisory Board held in the context of the European Society of Organ Transplantation (Barcelona, 24-27 September 2017). Final results coming from 70 patients indicate that Inmunobiogram® has shown the ability to measure the sensitivity of patients to Immunosuppressant medication (IMS), and on top of that, it can detect patients with bad prognosis due to IMS low sensitivity. The classification of immunoassay profiles, initially done by an expert, can be reproduced quite accurately by a neural network and thus completely automatized.

TRANSBIO clinical study is an international (European and USA), multicenter, evaluation of the clinical consistency and analytical robustness of Immunobiogram® as an In Vitro Diagnostics BIOtechnological Tool to help decision-making in adjustment of immunosuppressant therapy for Renal TRANSplant. Transbio study is beginning in April 2018 and it is expected to give conclusive results in 2019.

  • PoC
  • Feasibility
  • Sensitivity grade patterns
  • Correlation of Inmunobiogram sensitivity patterns with clinical evolution.
  • Robustness of Inmunobiogram bioassay
  • Confirm correlation between Inmunobiogram sensitivity patterns and clinical evolutionand clinical evolution

Only a conventional 10mL blood sample from the patient is needed to run the immunoassay. It is based on 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. IMBG allows for a direct comparison between several immunosuppressant drugs in terms of immunosuppressive potency for each specific patient at the time the immunoassay is run. As the immunological system is very dynamic and can be affected by many factors, it is anticipated that Inmunobiogram® would be better used as a test to monitor patient´s intrinsic response to immunosuppressant drugs over time.

Current drugs tested in Inmunobiogram® – Transplant are:

CNI – inhibitors
Antiproliferative agents
mTOR inhibitors
Corticoids

Tacrolimus

Mycophenolic acid

Sirolimus

Metilprednisolone

Ciclosporin

Azathioprin

Everolimus

 

Inmunobiogram® is an In Vitro Diagnostic laboratory test that combines a biotechnological KIT and a software for data interpretation. Inmunobiogram® bioassay is to be read with a luminometer or similar device. An automatic mathematical algorithm has been developed that, using rough data directly coming from the luminometer, offers a SCORE that evaluates patient´s individual sensitivity to the immunosuppressant panel of drugs. Due to its design and easy-to-read output, we anticipate it will be easily used in the clinical setting.

A European patent was presented in 2017 to protect this invention.

BH-Pilot Study

BH-Pilot study included 70 patients from “La Paz” and “Puerta de Hierro” University Hospitals (Madrid), classified into three categories depending on an immunological risk evaluation:

  • High-risk patients (with a history of rejection, positive antibodies or impaired renal function, or combinations of previous criteria)
  • Controlled patients (with conventional maintenance immunosuppression)
  • Low-risk patients (without risk criteria and low levels of medication for years).

Data on patients’ clinical and immunological history have been collected; an extensive battery of biomarkers has been performed on different platforms to complement the risk information, and 10Ml of blood has been taken to be tested at INMUNOBIOGRAM®.

Final results with the INMUNOBIOGRAM®, obtained in blood samples from 69 kidney transplanted patients and 7 healthy volunteers as a control group, clearly indicate a positive proof of concept.

The observed data can be summarized in the following points:

 

1) The INMUNOBIOGRAM® provides an individualized patient response pattern to immunosuppressive medication.

2) Sensitivity ranges can be determined in each patient for each of the drugs tested.

3) Significantly associated low-sensitivity patterns have been observed in patients who present worse clinical evolution and also receive higher doses of medication. These low-sensitivity patterns actually are more prominent to those drugs that patients are currently taking. On the contrary, patients with a low-risk profile show better sensitivity scores in Inmunobiogram® compared with standard patients and high-risk patients.

In this clinical study, Inmunobiogram® has shown the ability to measure the sensitivity of patients to Immunosuppressant medication (IMS), and on top of that, it can detect patients with bad prognosis due to IMS low sensitivity. The classification of immunoassay profiles, initially done by an expert, can be reproduced quite accurately by a neural network and thus completely automatized.

UE flag

 “This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 733248”

 “This information reflects only Biohope’s view; the Agency is not responsible for any use that may be made of the information it contains herein”.