Tissue cross-reactivity (TCR) studies are basically screening assays that are used to identify the non-specific and specific binding of test biologics, such as antibodies or antibody-like proteins in different types of human or animal tissues. A TCR study is vital in the development of monoclonal antibodies and other related issues, to ascertain that experimental antibodies do not bind to epitopes other than the targeted sites. This is done to ensure that treatment-related toxicity does not occur.
Read on to know everything about how laboratories conduct TCR analysis and the wide range of TCR services offered by them.
Tissue Cross-Reactivity Study: An Introduction
Generally, a TCR study is done through immunohistochemistry (IHC). The test biologic is a panel of tissues from human or animal species that have been selected for the purpose of evaluating toxicity. In several cases, the staining profiles of animal and human tissues on a test biologic may vary in terms of intensity and distribution. This suggests that the data from a TCR study should be interpreted carefully and on a case-by-case basis in the context of preclinical studies.
TCR studies are very useful in the identification of target organs and target species for toxicology studies. When human tissues are used, the primary goal is the potential identification of cross-reactive and off-target epitopes across a range of tissues. In the case of animal tissues, a TCR study helps in the identification of the most relevant species that have a target expression profile similar to that of humans.
The Importance of Tissue Cross-Reactivity Studies
So why are TCR studies important? They are needed because they are used to support human clinical trials. The process is initiated when a clinical trial application is filed with regulatory authorities for a test biologic. TCR studies form an essential component of the preclinical safety assessment package that is generally offered by laboratories.
The staining pattern and the distribution of staining on the human tissue panel alert investigators to the potential toxicity towards some targeted organs. It also has the possibility of expanding the potential indications that have not been previously identified.
As the primary goal is safety assessment, the intensity of the staining can provide valuable insights into the potential toxicity. Along with data from animal tissue, TCR studies help in the determination of the right kind of species to perform in-vivo toxicity studies to obtain helpful qualitative information on the effect of cross-reacting biologics.
The Applications of Tissue Cross-Reactivity
There are various applications of a TCR analysis. They include:
- Determining potential risks in patients
- Compiling a complete tissue bank of a wide variety of species that include infected tumours and tissues, fixed or frozen tissues and in vivo studies
- Generating high-quality audited reports
- Digital photomicroscopy
- Quality assurance
- Critical phase audits
- Efficient reporting and scheduling
- Preparation of study-specific protocols for exact requirements
Tissue Cross-Reactivity Services Offered by Laboratories
Many laboratories provide immunohistochemistry-based tissue cross-reactivity (TCR) studies in compliance with GLP regulations. Some of the TCR services offered are listed below:
- Preliminary studies
- Definitive studies: antibody concentrations, tissues and subjects
- Evaluation of slides and interpretation
- In vitro cross-reactivity
- In vivo binding of test articles
- TCR analysis of potential treatment-related effects
- Preclinical monoclonal safety
- Clinical trial support: entry criteria, biomarkers
- Final report
In conclusion, a tissue cross-reactivity study helps in a better understanding of the difference and similarities of drug target localization as well as the expression between various species. Many laboratories use the Leica Bond-III system that is known for its consistent and reliable results.