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dc.contributor.authorEigenmann, Miro Julian
dc.contributor.authorKarlsen, Tine Veronica
dc.contributor.authorWagner, Marek
dc.contributor.authorTenstad, Olav
dc.contributor.authorWeinzierl, Tina
dc.contributor.authorFauti, Tanja
dc.contributor.authorGrimm, Hans Peter
dc.contributor.authorSkogstrand, Trude
dc.contributor.authorKlein, Christian
dc.contributor.authorSam, Johannes
dc.contributor.authorUmana, Pablo
dc.contributor.authorBacac, Marina
dc.contributor.authorWiig, Helge
dc.contributor.authorWalz, Antje-Christine
dc.date.accessioned2022-04-07T06:26:38Z
dc.date.available2022-04-07T06:26:38Z
dc.date.created2022-01-29T21:29:45Z
dc.date.issued2021
dc.identifier.issn1999-4923
dc.identifier.urihttps://hdl.handle.net/11250/2990328
dc.description.abstractThe goal of this study is to investigate the pharmacokinetics in plasma and tumour interstitial fluid of two T-cell bispecifics (TCBs) with different binding affinities to the tumour target and to assess the subsequent cytokine release in a tumour-bearing humanised mouse model. Pharmacokinetics (PK) as well as cytokine data were collected in humanised mice after iv injection of cibisatamab and CEACAM5-TCB which are binding with different binding affinities to the tumour antigen carcinoembryonic antigen (CEA). The PK data were modelled and coupled to a previously published physiologically based PK model. Corresponding cytokine release profiles were compared to in vitro data. The PK model provided a good fit to the data and precise estimation of key PK parameters. High tumour interstitial concentrations were observed for both TCBs, influenced by their respective target binding affinities. In conclusion, we developed a tailored experimental method to measure PK and cytokine release in plasma and at the site of drug action, namely in the tumour. Integrating those data into a mathematical model enabled to investigate the impact of target affinity on tumour accumulation and can have implications for the PKPD assessment of the therapeutic antibodies.en_US
dc.language.isoengen_US
dc.publisherMDPIen_US
dc.rightsNavngivelse 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/deed.no*
dc.titlePharmacokinetics and pharmacodynamics of t-cell bispecifics in the tumour interstitial fluiden_US
dc.typeJournal articleen_US
dc.typePeer revieweden_US
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2021 by the authorsen_US
dc.source.articlenumber2105en_US
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1
dc.identifier.doi10.3390/pharmaceutics13122105
dc.identifier.cristin1993282
dc.source.journalPharmaceuticsen_US
dc.identifier.citationPharmaceutics. 2021, 13 (12), 2105.en_US
dc.source.volume13en_US
dc.source.issue12en_US


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