Bibliographic Details
| Title: |
Implementation of Systematic Bioanalysis of Antibody–Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats. |
| Authors: |
Jeon, Eun-Jeong, Han, Ju-Hee, Seo, Youjin, Koh, Eun Mi, Han, Kang-Hyun, Hwang, Kyunghwa, Jung, Kyung Jin |
| Source: |
Pharmaceutics; Mar2023, Vol. 15 Issue 3, p756, 13p |
| Subject Terms: |
ANTIBODY-drug conjugates, HER2 positive breast cancer, DRUG stability, MONOCLONAL antibodies, PHARMACOKINETICS, ENZYME-linked immunosorbent assay, TRASTUZUMAB |
| Company/Entity: |
UNITED States. Food & Drug Administration |
| Abstract: |
Antibody–drug conjugates (ADCs) are composed of monoclonal antibodies covalently bound to cytotoxic drugs by a linker. They are designed to selectively bind target antigens and present a promising cancer treatment without the debilitating side effects of conventional chemotherapies. Ado-trastuzumab emtansine (T-DM1) is an ADC that received US FDA approval for the treatment of HER2-positive breast cancer. The purpose of this study was to optimize methods for the quantification of T-DM1 in rats. We optimized four analytical methods: (1) an enzyme-linked immunosorbent assay (ELISA) to quantify the total trastuzumab levels in all drug-to-antibody ratios (DARs), including DAR 0; (2) an ELISA to quantify the conjugated trastuzumab levels in all DARs except DAR 0; (3) an LC–MS/MS analysis to quantify the levels of released DM1; and (4) a bridging ELISA to quantify the level of anti-drug antibodies (ADAs) of T-DM1. We analyzed serum and plasma samples from rats injected intravenously with T-DM1 (20 mg/kg, single dose) using these optimized methods. Based on these applied analytical methods, we evaluated the quantification, pharmacokinetics, and immunogenicity of T-DM1. This study establishes the systematic bioanalysis of ADCs with validated assays, including drug stability in matrix and ADA assay, for future investigation on the efficacy and safety of ADC development. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
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