FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4308678863> ?p ?o ?g. }

• W4308678863 endingPage "1101" @default.
• W4308678863 startingPage "1086" @default.
• W4308678863 abstract "We evaluated the activity of AZD8205, a B7-H4-directed antibody-drug conjugate (ADC) bearing a novel topoisomerase I inhibitor (TOP1i) payload, alone and in combination with the PARP1-selective inhibitor AZD5305, in preclinical models.IHC and deep-learning-based image analysis algorithms were used to assess prevalence and intratumoral heterogeneity of B7-H4 expression in human tumors. Several TOP1i-ADCs, prepared with Val-Ala or Gly-Gly-Phe-Gly peptide linkers, with or without a PEG8 spacer, were compared in biophysical, in vivo efficacy, and rat toxicology studies. AZD8205 mechanism of action and efficacy studies were conducted in human cancer cell line and patient-derived xenograft (PDX) models.Evaluation of IHC-staining density on a per-cell basis revealed a range of heterogeneous B7-H4 expression across patient tumors. This informed selection of bystander-capable Val-Ala-PEG8-TOP1i payload AZ14170133 and development of AZD8205, which demonstrated improved stability, efficacy, and safety compared with other linker-payload ADCs. In a study of 26 PDX tumors, single administration of 3.5 mg/kg AZD8205 provided a 69% overall response rate, according to modified RECIST criteria, which correlated with homologous recombination repair (HRR) deficiency (HRD) and elevated levels of B7-H4 in HRR-proficient models. Addition of AZD5305 sensitized very low B7-H4-expressing tumors to AZD8205 treatment, independent of HRD status and in models representing clinically relevant mechanisms of PARPi resistance.These data provide evidence for the potential utility of AZD8205 for treatment of B7-H4-expressing tumors and support the rationale for an ongoing phase 1 clinical study (NCT05123482). See related commentary by Pommier and Thomas, p. 991." @default.
• W4308678863 created "2022-11-14" @default.
• W4308678863 creator A5000709034 @default.
• W4308678863 creator A5008491342 @default.
• W4308678863 creator A5011515348 @default.
• W4308678863 creator A5012180250 @default.
• W4308678863 creator A5012679547 @default.
• W4308678863 creator A5014632539 @default.
• W4308678863 creator A5014960774 @default.
• W4308678863 creator A5019757898 @default.
• W4308678863 creator A5019871681 @default.
• W4308678863 creator A5040578796 @default.
• W4308678863 creator A5041289414 @default.
• W4308678863 creator A5043655203 @default.
• W4308678863 creator A5044830291 @default.
• W4308678863 creator A5045599189 @default.
• W4308678863 creator A5048240683 @default.
• W4308678863 creator A5050637005 @default.
• W4308678863 creator A5051368970 @default.
• W4308678863 creator A5052678820 @default.
• W4308678863 creator A5053107298 @default.
• W4308678863 creator A5056326026 @default.
• W4308678863 creator A5058444974 @default.
• W4308678863 creator A5070406189 @default.
• W4308678863 creator A5071770314 @default.
• W4308678863 creator A5072096816 @default.
• W4308678863 creator A5073559624 @default.
• W4308678863 creator A5076501775 @default.
• W4308678863 creator A5076745184 @default.
• W4308678863 creator A5078346499 @default.
• W4308678863 creator A5079106715 @default.
• W4308678863 creator A5085246912 @default.
• W4308678863 creator A5086547100 @default.
• W4308678863 creator A5091035527 @default.
• W4308678863 date "2022-11-10" @default.
• W4308678863 modified "2023-10-16" @default.
• W4308678863 title "Design and Preclinical Evaluation of a Novel B7-H4–Directed Antibody–Drug Conjugate, AZD8205, Alone and in Combination with the PARP1-Selective Inhibitor AZD5305" @default.
• W4308678863 doi "https://doi.org/10.1158/1078-0432.ccr-22-2630" @default.
• W4308678863 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36355054" @default.
• W4308678863 hasPublicationYear "2022" @default.
• W4308678863 type Work @default.
• W4308678863 citedByCount "7" @default.
• W4308678863 countsByYear W43086788632023 @default.
• W4308678863 crossrefType "journal-article" @default.
• W4308678863 hasAuthorship W4308678863A5000709034 @default.
• W4308678863 hasAuthorship W4308678863A5008491342 @default.
• W4308678863 hasAuthorship W4308678863A5011515348 @default.
• W4308678863 hasAuthorship W4308678863A5012180250 @default.
• W4308678863 hasAuthorship W4308678863A5012679547 @default.
• W4308678863 hasAuthorship W4308678863A5014632539 @default.
• W4308678863 hasAuthorship W4308678863A5014960774 @default.
• W4308678863 hasAuthorship W4308678863A5019757898 @default.
• W4308678863 hasAuthorship W4308678863A5019871681 @default.
• W4308678863 hasAuthorship W4308678863A5040578796 @default.
• W4308678863 hasAuthorship W4308678863A5041289414 @default.
• W4308678863 hasAuthorship W4308678863A5043655203 @default.
• W4308678863 hasAuthorship W4308678863A5044830291 @default.
• W4308678863 hasAuthorship W4308678863A5045599189 @default.
• W4308678863 hasAuthorship W4308678863A5048240683 @default.
• W4308678863 hasAuthorship W4308678863A5050637005 @default.
• W4308678863 hasAuthorship W4308678863A5051368970 @default.
• W4308678863 hasAuthorship W4308678863A5052678820 @default.
• W4308678863 hasAuthorship W4308678863A5053107298 @default.
• W4308678863 hasAuthorship W4308678863A5056326026 @default.
• W4308678863 hasAuthorship W4308678863A5058444974 @default.
• W4308678863 hasAuthorship W4308678863A5070406189 @default.
• W4308678863 hasAuthorship W4308678863A5071770314 @default.
• W4308678863 hasAuthorship W4308678863A5072096816 @default.
• W4308678863 hasAuthorship W4308678863A5073559624 @default.
• W4308678863 hasAuthorship W4308678863A5076501775 @default.
• W4308678863 hasAuthorship W4308678863A5076745184 @default.
• W4308678863 hasAuthorship W4308678863A5078346499 @default.
• W4308678863 hasAuthorship W4308678863A5079106715 @default.
• W4308678863 hasAuthorship W4308678863A5085246912 @default.
• W4308678863 hasAuthorship W4308678863A5086547100 @default.
• W4308678863 hasAuthorship W4308678863A5091035527 @default.
• W4308678863 hasConcept C121608353 @default.
• W4308678863 hasConcept C126322002 @default.
• W4308678863 hasConcept C134306372 @default.
• W4308678863 hasConcept C142724271 @default.
• W4308678863 hasConcept C150903083 @default.
• W4308678863 hasConcept C159654299 @default.
• W4308678863 hasConcept C197336794 @default.
• W4308678863 hasConcept C203014093 @default.
• W4308678863 hasConcept C204232928 @default.
• W4308678863 hasConcept C207001950 @default.
• W4308678863 hasConcept C2777092746 @default.
• W4308678863 hasConcept C2777325958 @default.
• W4308678863 hasConcept C2781197716 @default.
• W4308678863 hasConcept C33923547 @default.
• W4308678863 hasConcept C502942594 @default.
• W4308678863 hasConcept C542903549 @default.
• W4308678863 hasConcept C55493867 @default.
• W4308678863 hasConcept C71924100 @default.
• W4308678863 hasConcept C86803240 @default.
• W4308678863 hasConcept C98274493 @default.
• W4308678863 hasConceptScore W4308678863C121608353 @default.
• W4308678863 hasConceptScore W4308678863C126322002 @default.

• next