Tissue cross-reactivity studies of CPGJ701 in humans, cynomolgus monkeys and Sprague-Dawley rats and correlation analysis with in vivo toxicity

• DOI: 10.21037/atm.2020.02.106
• Publication Date: 2020-03-31T03:48:46Z
• Authors: Zhe Qu; Jianjun Lyu; Yue Liu; Xin Wang; Zhi Lin; Yanwei Yang; Di Zhang; Xingchao Geng; Bo Li
• Keywords: Ex vivo

Background: CPGJ701 is a recombinant humanized anti-human epidermal growth factor receptor-2 (HER2) monoclonal antibody-derivative of the cytotoxic agent maytansine (DM1) conjugate for treatment HER2-positive metastatic breast cancer. Tissue cross-reactivity (TCR) studies in complete panel normal human, cynomolgus monkey and Sprague-Dawley were performed to provide evidence selecting animal species use preclinical toxicity predicting primary target organs clinical adverse drug reactions (ADRs). Methods: TCR carried out evaluate distribution reactivity paraffin sections 32 tissues and/or (such as heart, lung, liver, kidney) from at least three unrelated rat donors. The CPGJ701was detected by one-step immunohistochemical method using 50 µg/mL biotin-labeled antibody. Moreover, negative human IgG control group, blank phosphate-buffered saline (PBS) positive cancer tissue group also used exclude false results. specific binding humans, monkeys rats under microscope. Results: humans was highly consistent but showed some differences compared rats. tissues, such adrenal gland, thyroid, fallopian tube, spinal cord skin, observed not Specific placenta only found cell types which specifically bound, including epithelial cells, cardiomyocytes nerve identical Conclusions: accord with targeting characteristics anti-HER2 consistency indicated that relevant evaluating safety CPGJ701. (binding site) it useful antibody-dependent non-antibody-dependent toxicity. In conclusion, these could information nonclinical ADRs.