Implementation of Systematic Bioanalysis of Antibody–Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats.
| 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] |
| Copyright of Pharmaceutics is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Complementary Index |
| Full text is not displayed to guests. | Login for full access. |
| FullText | Links: – Type: pdflink Text: Availability: 1 CustomLinks: – Url: https://resolver.ebsco.com/c/xy5jbn/result?sid=EBSCO:edb&genre=article&issn=19994923&ISBN=&volume=15&issue=3&date=20230301&spage=756&pages=756-768&title=Pharmaceutics&atitle=Implementation%20of%20Systematic%20Bioanalysis%20of%20Antibody%E2%80%93Drug%20Conjugates%20for%20Preclinical%20Pharmacokinetic%20Study%20of%20Ado-Trastuzumab%20Emtansine%20%28T-DM1%29%20in%20Rats.&aulast=Jeon%2C%20Eun-Jeong&id=DOI:10.3390/pharmaceutics15030756 Name: Full Text Finder (for New FTF UI) (s8985755) Category: fullText Text: Find It @ SCU Libraries MouseOverText: Find It @ SCU Libraries |
|---|---|
| Header | DbId: edb DbLabel: Complementary Index An: 162816183 RelevancyScore: 965 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 965.414245605469 |
| IllustrationInfo | |
| Items | – Name: Title Label: Title Group: Ti Data: Implementation of Systematic Bioanalysis of Antibody–Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Jeon%2C+Eun-Jeong%22">Jeon, Eun-Jeong</searchLink><br /><searchLink fieldCode="AR" term="%22Han%2C+Ju-Hee%22">Han, Ju-Hee</searchLink><br /><searchLink fieldCode="AR" term="%22Seo%2C+Youjin%22">Seo, Youjin</searchLink><br /><searchLink fieldCode="AR" term="%22Koh%2C+Eun+Mi%22">Koh, Eun Mi</searchLink><br /><searchLink fieldCode="AR" term="%22Han%2C+Kang-Hyun%22">Han, Kang-Hyun</searchLink><br /><searchLink fieldCode="AR" term="%22Hwang%2C+Kyunghwa%22">Hwang, Kyunghwa</searchLink><br /><searchLink fieldCode="AR" term="%22Jung%2C+Kyung+Jin%22">Jung, Kyung Jin</searchLink> – Name: TitleSource Label: Source Group: Src Data: Pharmaceutics; Mar2023, Vol. 15 Issue 3, p756, 13p – Name: Subject Label: Subject Terms Group: Su Data: <searchLink fieldCode="DE" term="%22ANTIBODY-drug+conjugates%22">ANTIBODY-drug conjugates</searchLink><br /><searchLink fieldCode="DE" term="%22HER2+positive+breast+cancer%22">HER2 positive breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22DRUG+stability%22">DRUG stability</searchLink><br /><searchLink fieldCode="DE" term="%22MONOCLONAL+antibodies%22">MONOCLONAL antibodies</searchLink><br /><searchLink fieldCode="DE" term="%22PHARMACOKINETICS%22">PHARMACOKINETICS</searchLink><br /><searchLink fieldCode="DE" term="%22ENZYME-linked+immunosorbent+assay%22">ENZYME-linked immunosorbent assay</searchLink><br /><searchLink fieldCode="DE" term="%22TRASTUZUMAB%22">TRASTUZUMAB</searchLink> – Name: SubjectCompany Label: Company/Entity Group: Su Data: <searchLink fieldCode="CO" term="%22UNITED+States%2E+Food+%26+Drug+Administration%22">UNITED States. Food & Drug Administration</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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] – Name: Abstract Label: Group: Ab Data: <i>Copyright of Pharmaceutics is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://login.libproxy.scu.edu/login?url=https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&scope=site&db=edb&AN=162816183 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.3390/pharmaceutics15030756 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 13 StartPage: 756 Subjects: – SubjectFull: UNITED States. Food & Drug Administration Type: general – SubjectFull: ANTIBODY-drug conjugates Type: general – SubjectFull: HER2 positive breast cancer Type: general – SubjectFull: DRUG stability Type: general – SubjectFull: MONOCLONAL antibodies Type: general – SubjectFull: PHARMACOKINETICS Type: general – SubjectFull: ENZYME-linked immunosorbent assay Type: general – SubjectFull: TRASTUZUMAB Type: general Titles: – TitleFull: Implementation of Systematic Bioanalysis of Antibody–Drug Conjugates for Preclinical Pharmacokinetic Study of Ado-Trastuzumab Emtansine (T-DM1) in Rats. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Jeon, Eun-Jeong – PersonEntity: Name: NameFull: Han, Ju-Hee – PersonEntity: Name: NameFull: Seo, Youjin – PersonEntity: Name: NameFull: Koh, Eun Mi – PersonEntity: Name: NameFull: Han, Kang-Hyun – PersonEntity: Name: NameFull: Hwang, Kyunghwa – PersonEntity: Name: NameFull: Jung, Kyung Jin IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2023 Type: published Y: 2023 Identifiers: – Type: issn-print Value: 19994923 Numbering: – Type: volume Value: 15 – Type: issue Value: 3 Titles: – TitleFull: Pharmaceutics Type: main |
| ResultId | 1 |