The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies
Dose selection for first-in-human (FIH) clinical trials with monoclonal antibodies (mAbs) is based on specifically designed preclinical pharmacology and toxicology studies, mechanistic ex vivo / in vitro investigations with human and animal cells and pharmacokinetic/pharmacodynamic (PK/PD) modeling...
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| Veröffentlicht in: | Current opinion in biotechnology 2009-12, Vol.20 (6), p.722-729 |
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| container_title | Current opinion in biotechnology |
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| creator | Muller, Patrick Y Milton, Mark Lloyd, Peter Sims, Jennifer Brennan, Frank R |
| description | Dose selection for first-in-human (FIH) clinical trials with monoclonal antibodies (mAbs) is based on specifically designed preclinical pharmacology and toxicology studies, mechanistic ex vivo / in vitro investigations with human and animal cells and pharmacokinetic/pharmacodynamic (PK/PD) modeling approaches and requires a thorough understanding of the biology of the target and the relative binding and pharmacological activity of the mAb in animals and humans. These investigations provide the essential information required for the selection of a safe starting dose and escalation for FIH trials based on toxicology and pharmacology data and the minimal anticipated biological effect level (MABEL) by integrating all available in vivo and in vitro data. In this review, strategies for estimation of the MABEL for mAbs specific for both membrane and soluble targets are presented and the scientific and regulatory challenges highlighted. |
| doi_str_mv | 10.1016/j.copbio.2009.10.013 |
| format | Article |
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In this review, strategies for estimation of the MABEL for mAbs specific for both membrane and soluble targets are presented and the scientific and regulatory challenges highlighted.</description><subject>Animals</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - chemistry</subject><subject>Biopharmaceutics - methods</subject><subject>Cell Membrane</subject><subject>Clinical Trials as Topic</subject><subject>Computer Simulation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Evaluation, Preclinical</subject><subject>Humans</subject><subject>Immunologic Factors - administration & dosage</subject><subject>Internal Medicine</subject><subject>Models, Biological</subject><subject>Models, Theoretical</subject><subject>Pharmaceutical Preparations - administration & dosage</subject><subject>Pharmaceutical Preparations - metabolism</subject><subject>Research Design</subject><issn>0958-1669</issn><issn>1879-0429</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFksFu1DAQhi0EotvCGyDkE4LDLmM7ceILUlu1gLSIA-VsOc6Y9eLEi50U9Ql4bRztIiQunCyN__lG8_9DyAsGGwZMvt1vbDx0Pm44gCqlDTDxiKxY26g1VFw9JitQdbtmUqozcp7zHgBq0cBTcsZUq2TL6xX5dbdDOvjRD_NAzTh56w9mwp4WcojfvDWBonNoJxrwHgN9_eny6mb7hrqYaMZQPnwcaXTU-ZQnupsHM9I-ZqR-pDYU8oKYkjch059-2tEhjtGGOJbyMrCLvcf8jDxxRYHPT-8F-Xp7c3f9Yb39_P7j9eV2bauqmdaKN8K0hgE3yvC6kWX31slaVFbyinVCYNvUleqNM4J3DqHrmZMSpBR129Xigrw6cg8p_pgxT3rw2WIIZsQ4Z80Zk20Nsgiro9CmmHNCpw_JDyY9aAZ6CUDv9TEAvQSwVEsApe3liT93A_Z_m06OF8G7owDLlvcek87W42ix96mYqfvo_zfhX8Afl7_jA-Z9nFOxNmumM9egvyxHsNwAKABWsUr8Bnlbro8</recordid><startdate>20091201</startdate><enddate>20091201</enddate><creator>Muller, Patrick Y</creator><creator>Milton, Mark</creator><creator>Lloyd, Peter</creator><creator>Sims, Jennifer</creator><creator>Brennan, Frank R</creator><general>Elsevier Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope></search><sort><creationdate>20091201</creationdate><title>The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies</title><author>Muller, Patrick Y ; Milton, Mark ; Lloyd, Peter ; Sims, Jennifer ; Brennan, Frank R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c447t-9273a8a102a9a25760098f6534c6241b33e87549dafa32bfe0bd1f66066358b53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - chemistry</topic><topic>Biopharmaceutics - methods</topic><topic>Cell Membrane</topic><topic>Clinical Trials as Topic</topic><topic>Computer Simulation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Evaluation, Preclinical</topic><topic>Humans</topic><topic>Immunologic Factors - administration & dosage</topic><topic>Internal Medicine</topic><topic>Models, Biological</topic><topic>Models, Theoretical</topic><topic>Pharmaceutical Preparations - administration & dosage</topic><topic>Pharmaceutical Preparations - metabolism</topic><topic>Research Design</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Muller, Patrick Y</creatorcontrib><creatorcontrib>Milton, Mark</creatorcontrib><creatorcontrib>Lloyd, Peter</creatorcontrib><creatorcontrib>Sims, Jennifer</creatorcontrib><creatorcontrib>Brennan, Frank R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><jtitle>Current opinion in biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Muller, Patrick Y</au><au>Milton, Mark</au><au>Lloyd, Peter</au><au>Sims, Jennifer</au><au>Brennan, Frank R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies</atitle><jtitle>Current opinion in biotechnology</jtitle><addtitle>Curr Opin Biotechnol</addtitle><date>2009-12-01</date><risdate>2009</risdate><volume>20</volume><issue>6</issue><spage>722</spage><epage>729</epage><pages>722-729</pages><issn>0958-1669</issn><eissn>1879-0429</eissn><abstract>Dose selection for first-in-human (FIH) clinical trials with monoclonal antibodies (mAbs) is based on specifically designed preclinical pharmacology and toxicology studies, mechanistic ex vivo / in vitro investigations with human and animal cells and pharmacokinetic/pharmacodynamic (PK/PD) modeling approaches and requires a thorough understanding of the biology of the target and the relative binding and pharmacological activity of the mAb in animals and humans. 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| identifier | ISSN: 0958-1669 |
| ispartof | Current opinion in biotechnology, 2009-12, Vol.20 (6), p.722-729 |
| issn | 0958-1669 1879-0429 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - chemistry Biopharmaceutics - methods Cell Membrane Clinical Trials as Topic Computer Simulation Dose-Response Relationship, Drug Drug Evaluation, Preclinical Humans Immunologic Factors - administration & dosage Internal Medicine Models, Biological Models, Theoretical Pharmaceutical Preparations - administration & dosage Pharmaceutical Preparations - metabolism Research Design |
| title | The minimum anticipated biological effect level (MABEL) for selection of first human dose in clinical trials with monoclonal antibodies |
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