Tissue cross reactivity (TCR)

It is expected that for an IND/CTA submission for most biotherapeutics, a TCR study is conducted to primarily identify off-target binding, but also to pick up previously unknown sites of on-target binding.  Such a study can be used to give an indication of potential organ toxicity in vivo and also to compare patterns of staining between human and animal tissue, providing additional justification for the choice of animal toxicity models used to generate other pre-clinical safety data.

TCR studies are conducted at labcorp sites based in the United Kingdom at both Harrogate and Huntingdon.  Both sites belong to the UK GLP compliance monitoring program, run by the UK GLP Monitoring Authority (UK GLPMA) which is part of the Medicines and Healthcare Products Regulatory Authority (MHRA). 

Both the Harrogate and Huntingdon sites have been performing these studies since 1997. Dedicated teams of scientists with immunohistochemistry (IHC) and histology experience are involved in all aspects of the study to ensure IHC staining protocols are optimized to generate and deliver meaningful data. 

For human TCR studies, labcorp has access to all the frozen tissues as per the US FDA and EMA requirements.  Both sites are licensed by the United Kingdom Human Tissue Authority (UK HTA).  For animal species TCR studies, labcorp has frozen tissues from all the most frequently used toxicology models (Primate, Mini-Pig, Dog, Rodent). 

Custom antibody labelling procedures (e.g. Biotin, FITC, Alexa488) can be performed if required.  Pre-complex procedures can also be used if labelling procedures are not deemed appropriate.  We appreciate that test article quantities may be limited and while ideally a minimum of 30 mgs is requested for labeling procedures, if necessary we can work with significantly less test article quantities. We are happy to discuss other test article requirements for your TCR study further.

The time required to complete a TCR study depends on the IHC protocol development and optimization stage.  Development and optimization of a suitable and robust IHC protocol is typically completed within 6 weeks.  Draft data/report from the TCR assessment is typically available within a further 6 weeks following successful development and optimization of the IHC staining protocol.

Experienced pathologists review all TCR studies.  Pathologists are available to discuss the results during all stages of the study from IHC staining protocol development/optimization through to the tissue panel staining.  Staining intensity, cellular location, tissue distribution and frequency of staining are routinely recorded; however, we are happy to discuss inclusion of additional specific pathology endpoint criteria.