TISSUE DAMAGE STUDIES

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 RESEARCH

& PREDICTING IMMUNE RISK

Acquiring critical information on the immunogenic property of a drug prior to clinical trials could be pivotal in avoiding patient risks and attrition due to costly drug failure. We bring a comprehensive meaning to immunogenicity and an innovative method of assessing immunologic risk. We emphasise on the analysis of drug-induced tissue damage. Immune response that may be generated from such damage could lead to serious drug adversity. We use an in vitro human platform analysing biomarkers of immune risk and response (adaptive) that can greatly contribute in predicting drug immunogenicity.

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Drug Immunogenicity

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 rather unclear 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 who have included recommendations for the testing of new biomarkers of immunogenic risk in their guidelines in recent years. Immundnz is constantly working to develop and bring new test systems (preclinical) to analyse drug immune risk 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

Tissue Damage & Immune Response Studies

At Immundnz we use standardised and customised assays based on 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 immune risk at preclinical stage. We can also develop cell systems of other mammals such as 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 or READ Technology.

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
  • 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

Tissue Damage Models

Conventionally drug induced damage to kidney and liver tissues is mostly studied in toxicology. Drugs are well known to cause damage to other organs upstream. We aim to provide human tissue models for testing drug-induced damage on vital systems such as:

  • Lungs/airway tissues
  • Cardiovascular system
  • Nervous system
  • Ophthalmic system
  • Intestinal tissue
  • Hepatic system
  • Renal system

These tissue models may be of cell line or primary cell origin and are designed to produce human data on damage under specific conditions. We are working to collaborate with esteemed laboratory groups around the world who have successfully established various tissue damage models that can generate similar or better results than in vivo models.

Study Process

  • In vitro cell systems representing human tissues of drug target sites
  • Drug challenge
  • Assessment of cell damage and cytotoxicity
  • Assessment of immunogenic by-products of tissue damage
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.

Some statistics……

  • >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