ABSTRACT
Tissue cross-reactivity (TCR) studies play an important role in the preclinical safety evaluation of monoclonal antibody (mAb) drugs.The objective of TCR studies is to find out off-target binding sites of mAbs,and provide valuable predictions for the toxicological evaluation and safety medication in vivo.According to the new drug application requirements of FDA,EMA and CFDA,TCR studies need to be carried out before Phase I clinic trails.As the origin of mAb drugs was transferred from murine antibodies to fully humanized antibodies in current years,immunohistochemical methods used in TCR studies were confronted with some new problems and challenges.Taking our own experiences and recent progress on TCR studies at home and abroad together,the authors summarized the recent exploration on technical difficulties of multipath system in TCR studies.This may provide valuable insight for further improving the quality of TCR studies and increase the predictive value of TCR studies for in vivo toxicological evaluation in China.