IMMUNE RISK ASSESSMENT
Can we avoid TeGenero-like scenarios and be better prepared rather than waiting for dangerous and disastrous outcomes to happen in the clinical phase? We can generate more critical information on drug immune safety in the preclinical phase that could be essential in the success of the drug.
MOVING TOWARDS TRANSLATIONAL IMMUNOTOXICOLOGY
& PREDICTIVE IMMUNOGENICITY
Acquiring critical information on immunogenic property of a drug prior to clinical trials could be pivotal in avoiding patient risks and attrition due to costly drug failure. Immundnz brings a very different meaning to immunogenicity and an innovative method of analysing immunologic risk. Within the context of immunotoxicology, our human cell based preclinical tests provide translational data based on novel biomarkers of immune response that can greatly contribute in predicting drug immunogenicity. Contact us for more information or READ MORE.
Much more than just antigenicity and ADAs
While conventional immunogenicity tests such as ADA and ‘cytokine storm’ tests provide valuable information on drug immunogenicity, much of the whole meaning of drug immunogenicity remains unknown hence the potential of a drug to cause immunogenicity remains untested. Immunogenicity is a much more complex issue and the scope of a drug to be immunogenic goes beyond its capacity to generate antibodies (antigenicity) through other immune pathways. In current immunology, the ‘self and non-self’ is a redundant theory and anything that can cause an immune response is immunogenic. A drug can be immunogenic by causing tissue damage (a tissue-directed path) and providing grounds for immunity against the tissue rather than the drug, i.e. drug induced immune response against organs. This is most likely the underlying mechanism of most drugs that cause autoimmunity and other secondary diseases. Conventional toxicology testing takes into account acute toxic damage and ignores moderate immune responses that might have pathological impact through progressive and chronic development.
This is a growing concern for the regulatory bodies which have inserted recommendations for testing of new biomarkers of immunogenic risk in their guidelines in recent years. Immundnz brings new test systems (preclinical) to analyse comprehensive drug immunogenicity in line with new regulatory recommendations.
- Robust and comprehensive immunologic profile: improved safety and risk prediction
- Reduced investments in non-viable drugs and reduced attrition rate
- Potential to improve drugs and make non-viable drugs accessible to patients
In Vitro Assays for Immunogenicity
At Immundnz we use standardised and customised assays based on immunology, molecular and protein biology, and human cell culture systems (cell lines, primary cells) to recapulate an in vitro immune microenviroment. Combined with cells of representative human organs (e.g. arteries/heart, lungs, kidney, liver, etc.) we use various lymphocytes such as dendritic cells, T cells, B cells, monocytes and macrophages. The aim is to provide you with valuable information on potential drug immunogenicity at preclinical stage. We can also develop cell systems of other mammal such rodents and bovids.
One of the key areas that we focus on is the assessment of drug-induced tissue damage leading to the possibility of chronic secondary immune-mediated pathology or immunotoxicity-mediated organ failure. Knowing about problems arising from drug-tissue interaction with the generation of immune response can be important in modifying drug pathway and preventing human risk in clinical treatment.
Contact us to know more about our assay services.
How Will You Benefit?
- Prediction of immune-mediated adverse drug reaction and avoiding risk in clinical phase
- Better translation from preclinical studies to humans
- Reduction of the number of animal tests
- A more robust and comprehensive immunologic profile: improved safety and risk prediction thus reducing human health hazard risk
- Drug development can be terminated before costly advanced stages of drug development: reduced investments in non-viable drugs and reduced attrition rate
- Potential to improve drugs, generate blocking agents against immune effectors and make non-viable drugs accessible to patients
- Meeting changes to regulatory requirements on immunologic safety
Drug Induced Secondary Pathology
There are many drugs in the market that are known to cause secondary disease. In many cases it is not known why the secondary adverse effect happens. The use of these drugs, in some cases on a wide scale, is due to their greater benefit of curing a life threatening condition. Autoimmunity is a common secondary pathology, and drug induced lupus (DIL) accounts for 10% of all lupus incidences.
We illustrate here the possible pathway of Interstitial Lung Disease caused by immune response against Amiodarone-induced damage of pneumocytes.
- >300 drugs are reported to cause Interstitial lung disease (DI-ILD)
- >2 million cases of adverse drug reactions in the US annually including 100,000 deaths
- 250,000 cases of hospital admissions in the UK annually
- €430M could be saved in the Netherlands if side effects are reduced
We are currently conducting a 2-year EU funded project, COMPIT, to research and develop a platform that enables the preclinical study of drug induced immunogenicity and the risk of immune mediated pathology. COMPIT, Comprehensive In Vitro Human Immune Response Testing of drug compounds, is a system of biological and analytical assays to study the interaction of a drug molecule with human tissues and assess drug induced adverse immune response that is generated through tissue damage. COMPIT is a preclinical system that can be applied to small molecules and large molecules. It integrates various immune and cellular assays available in our services currently and combines human cell lines, primary cells and 3D cultures to deliver an in vitro human cell-based immune system that recapitulates the in vivo human microenvironment. COMPIT fits into the current scheme of preclinical studies.
COMPIT can be applied to:
- Small molecule drugs
- Large molecule drugs
- Generics and biosimilars