Data Management And Sharing System of China National Clinical Research Center for Neurological Diseases
Preparation and anti-cancer evaluation of promiximab-MMAE, an anti-CD56 antibody drug conjugate, in small cell lung cancer cell line xenograft models
First author：Yu Lin
Corresponding author：Yang Jinliang
essential_information
2018-12-26
Published articles
Journal：Journal of Drug Targeting
Publication type: Article
IF(IF): 5.121
PMID: 29630426 Link To Pubmed Full text Download
Background And Purpose
Method
The average drug-to-antibody ratio (DAR) of Promiximab-MMAE was 3.13 as analysed by liquid chromatography-mass spectrometry/ mass spectrometry (LC-MS/MS). The targeting capacity and affinity kinetics of Promiximab-MMAE were similar to that of Promiximab after being conjugated with MMAE as tested by flow cytometry and biolayer interferometry analysis. Promiximab-MMAE showed effective anti-proliferation on CD56-positive cell lines (NCI-H524, NCI-H526, and NCI-H69), with the half maximal inhibitory concentration (IC50) values of 19.24, 5.23, and 0.32 nmol/L in vitro, respectively. Promiximab-MMAE of 10 mg/kg every three days with a total of three times was administered in vivo.
Conclusion
In conclusion, Promiximab-MMAE is a potential candidate for the treatment of CD56 positive small cell lung cancer.
Main results
Results showed that the tumour regression was not recrudesced in NCI-H69 and NCI-H526 xenograft mice models till 52 and 56 days. Moreover, body weight and histopathology of the major organs (liver, spleen, heart, lung, and kidney) showed no significant changes after treatment with Promiximab-MMAE.