Development, validation, and application of ELISA for detection of anti-HD105 antibodies in pre-clinical safety evaluation using monkeys
| Autor: | Sanghoon Lee, Hye Ryun Jo, Woo Hyuck Choi, Jang Su Jeon, Sang Kyum Kim, Eun-Jeong Jeon, Son Yonggyu, Woo Suk Koh, You Weonkyoo, So-Young Youm |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Chemistry Pharmaceutical Clinical Biochemistry Drug Evaluation Preclinical Pharmaceutical Science Enzyme-Linked Immunosorbent Assay Pharmacology Analytical Chemistry 03 medical and health sciences chemistry.chemical_compound Drug tolerance Drug Discovery Animals Humans Spectroscopy Autoantibodies biology Immunogenicity Autoantibody Antibodies Monoclonal Reproducibility of Results Assay sensitivity Vascular endothelial growth factor Macaca fascicularis 030104 developmental biology chemistry Toxicity biology.protein Clinical safety Female Antibody |
| Zdroj: | Journal of Pharmaceutical and Biomedical Analysis. 131:309-315 |
| ISSN: | 0731-7085 |
| DOI: | 10.1016/j.jpba.2016.09.009 |
| Popis: | Unwanted immunogenicity of protein therapeutics can result in severe side effects and should be assessed in animals before applying the treatment to humans. Monkeys are the most relevant choice for pre-clinical toxicity testing of antibody-based therapeutics. To assess the immunogenicity of HD105, a novel antibody therapeutic that targets both vascular endothelial growth factor and Delta-like-ligand 4, a bridging enzyme-linked immunosorbent assay was developed as an anti-drug antibody (ADA) assay and validated for use in pre-clinical studies using non-human primates. This method was found to have suitable assay sensitivity, intra- and inter-assay precision, confirmation, drug tolerance, recovery, and sample stability for measuring ADA in monkey serum samples. The results showed that ADA elevation occurred following repeated doses of HD105, and that ADA production was negatively associated with serum HD105 concentration. These results suggest that intravenous administration of HD105 induces production of ADA in monkeys and that the detection of ADA may be negatively influenced by free HD105 in serum. |
| Databáze: | OpenAIRE |
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