FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2167463450> ?p ?o ?g. }

• W2167463450 endingPage "2923" @default.
• W2167463450 startingPage "2913" @default.
• W2167463450 abstract "Abstract An anti-CD70 antibody conjugated to monomethylauristatin F (MMAF) via a valine-citrulline dipeptide containing linker has been shown previously to have potent antitumor activity in renal cell cancer xenograft studies. Here, we generated a panel of humanized anti-CD70 antibody IgG variants and conjugated them to MMAF to study the effect of isotype (IgG1, IgG2, and IgG4) and Fcγ receptor binding on antibody-drug conjugate properties. All IgG variants bound CD70+ 786-O cells with an apparent affinity of ∼1 nmol/L, and drug conjugation did not impair antigen binding. The parent anti-CD70 IgG1 bound to human FcγRI and FcγRIIIA V158 and mouse FcγRIV and this binding was not impaired by drug conjugation. In contrast, binding to these Fcγ receptors was greatly reduced or abolished in the variant, IgG1v1, containing the previously described mutations, E233P:L234V:L235A. All conjugates had potent cytotoxic activity against six different antigen-positive cancer cell lines in vitro with IC50 values of 30 to 540 pmol/L. The IgGv1 conjugate with MMAF displayed improved antitumor activity compared with other conjugates in 786-O and UMRC3 models of renal cell cancer and in the DBTRG05-MG glioblastoma model. All conjugates were tolerated to ≥40 mg/kg in mice. Thus, the IgG1v1 MMAF conjugate has an increased therapeutic index compared with the parent IgG1 conjugate. The improved antitumor activity of the IgG1v1 auristatin conjugates may relate to increased exposure as suggested by pharmacokinetic analysis. The strategy used here for enhancing the therapeutic index of antibody-drug conjugates is independent of the antigen-binding variable domains and potentially applicable to other antibodies. [Mol Cancer Ther 2008;7(9):2913–23]" @default.
• W2167463450 created "2016-06-24" @default.
• W2167463450 creator A5010371848 @default.
• W2167463450 creator A5025418128 @default.
• W2167463450 creator A5036332717 @default.
• W2167463450 creator A5037007713 @default.
• W2167463450 creator A5045436281 @default.
• W2167463450 creator A5046639473 @default.
• W2167463450 creator A5052067361 @default.
• W2167463450 creator A5053379518 @default.
• W2167463450 creator A5058357910 @default.
• W2167463450 creator A5063558583 @default.
• W2167463450 creator A5065128818 @default.
• W2167463450 creator A5072073795 @default.
• W2167463450 creator A5084792858 @default.
• W2167463450 creator A5084910442 @default.
• W2167463450 date "2008-09-01" @default.
• W2167463450 modified "2023-09-30" @default.
• W2167463450 title "Engineered anti-CD70 antibody-drug conjugate with increased therapeutic index" @default.
• W2167463450 cites W1032555108 @default.
• W2167463450 cites W1529809181 @default.
• W2167463450 cites W1557340160 @default.
• W2167463450 cites W1563403908 @default.
• W2167463450 cites W1686249017 @default.
• W2167463450 cites W1825768998 @default.
• W2167463450 cites W1966840924 @default.
• W2167463450 cites W1967113354 @default.
• W2167463450 cites W1993689954 @default.
• W2167463450 cites W1997422287 @default.
• W2167463450 cites W1997943615 @default.
• W2167463450 cites W1998744147 @default.
• W2167463450 cites W2001794353 @default.
• W2167463450 cites W2010147335 @default.
• W2167463450 cites W2023034663 @default.
• W2167463450 cites W2026462640 @default.
• W2167463450 cites W2037840717 @default.
• W2167463450 cites W2048313558 @default.
• W2167463450 cites W2050656150 @default.
• W2167463450 cites W2052789788 @default.
• W2167463450 cites W2083670340 @default.
• W2167463450 cites W2087638630 @default.
• W2167463450 cites W2093443171 @default.
• W2167463450 cites W2096387523 @default.
• W2167463450 cites W2124467421 @default.
• W2167463450 cites W2124532648 @default.
• W2167463450 cites W2129901781 @default.
• W2167463450 cites W2136101268 @default.
• W2167463450 cites W2144081223 @default.
• W2167463450 cites W2158285723 @default.
• W2167463450 cites W2166440745 @default.
• W2167463450 cites W2171368669 @default.
• W2167463450 doi "https://doi.org/10.1158/1535-7163.mct-08-0295" @default.
• W2167463450 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/18790772" @default.
• W2167463450 hasPublicationYear "2008" @default.
• W2167463450 type Work @default.
• W2167463450 sameAs 2167463450 @default.
• W2167463450 citedByCount "79" @default.
• W2167463450 countsByYear W21674634502012 @default.
• W2167463450 countsByYear W21674634502013 @default.
• W2167463450 countsByYear W21674634502014 @default.
• W2167463450 countsByYear W21674634502015 @default.
• W2167463450 countsByYear W21674634502016 @default.
• W2167463450 countsByYear W21674634502017 @default.
• W2167463450 countsByYear W21674634502018 @default.
• W2167463450 countsByYear W21674634502019 @default.
• W2167463450 countsByYear W21674634502020 @default.
• W2167463450 countsByYear W21674634502021 @default.
• W2167463450 countsByYear W21674634502022 @default.
• W2167463450 countsByYear W21674634502023 @default.
• W2167463450 crossrefType "journal-article" @default.
• W2167463450 hasAuthorship W2167463450A5010371848 @default.
• W2167463450 hasAuthorship W2167463450A5025418128 @default.
• W2167463450 hasAuthorship W2167463450A5036332717 @default.
• W2167463450 hasAuthorship W2167463450A5037007713 @default.
• W2167463450 hasAuthorship W2167463450A5045436281 @default.
• W2167463450 hasAuthorship W2167463450A5046639473 @default.
• W2167463450 hasAuthorship W2167463450A5052067361 @default.
• W2167463450 hasAuthorship W2167463450A5053379518 @default.
• W2167463450 hasAuthorship W2167463450A5058357910 @default.
• W2167463450 hasAuthorship W2167463450A5063558583 @default.
• W2167463450 hasAuthorship W2167463450A5065128818 @default.
• W2167463450 hasAuthorship W2167463450A5072073795 @default.
• W2167463450 hasAuthorship W2167463450A5084792858 @default.
• W2167463450 hasAuthorship W2167463450A5084910442 @default.
• W2167463450 hasBestOaLocation W21674634501 @default.
• W2167463450 hasConcept C109316439 @default.
• W2167463450 hasConcept C134306372 @default.
• W2167463450 hasConcept C153911025 @default.
• W2167463450 hasConcept C159654299 @default.
• W2167463450 hasConcept C185592680 @default.
• W2167463450 hasConcept C197336794 @default.
• W2167463450 hasConcept C19831878 @default.
• W2167463450 hasConcept C202751555 @default.
• W2167463450 hasConcept C203014093 @default.
• W2167463450 hasConcept C2777325958 @default.
• W2167463450 hasConcept C2780035454 @default.
• W2167463450 hasConcept C33923547 @default.
• W2167463450 hasConcept C542903549 @default.

• next