tailieunhanh - Báo cáo hóa học: " Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood"

Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood | Arai et al. Journal of Translational Medicine 2010 8 51 http content 8 1 51 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access Development and application of a biomarker assay for determining the pharmacodynamic activity of an antagonist candidate biotherapeutic antibody to IL21R in whole blood Maya Arai1 Sadhana Jain1 Amy A Weaver1 Andrew A Hill2 Yongjing Guo1 Andrea G Bree3 Michael F Smith Jr4 Scott W Allen5 Edward R LaVallie1 Deborah Young3 Laird Bloom1 Karissa Adkins6 and Margot O Toole 7 Abstract Background In preparation for potential clinical development of Ab-01 an antagonistic antibody directed against the IL21R studies were undertaken to address translational medicine needs that fall into four categories 1 development of a pharmacodynamic biomarker assay suitable for use in the clinic 2 demonstration that Ab-01 has the desired biological activity in vitro and in vivo in cynomolgus monkeys the preferred safety study species 3 pre-clinical in vivo proof-of-concept that the assay can be used to detect Ab-01 pharmacodynamic PD activity in treated subjects and 4 comprehensive assessment of the agonistic potential of Ab-01 when cross-linked. This report and a recently published companion report address the first three of these needs. The fourth has been addressed in a separate study. Methods Genes that change RNA expression upon ex vivo rhlL21 stimulation of whole blood were identified in human and cynomolgus monkey. The inhibitory effects of exogenously added Ab-01 were measured ex vivo in human and monkey and the in vivo inhibitory effects of Ab-01 treatment were measured in monkey. Results Stimulation of whole human blood for 2 hours with rhlL21 induced robust increases in RNA expression of 6 genes. This response was blocked by Ab-01 indicating that the assay is suitable for measuring Ab-01 activity in blood. rhlL21 induced expression of a similar set of genes in cynomolgus monkey blood. This response was blocked with Ab-01