FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2073496670> ?p ?o ?g. }

• W2073496670 abstract "One premise of antibody-drug conjugates (ADC) is that the bound mAb-antigen complex on the cell surface will internalize and be metabolized by lysosomal proteases to release the free drug. Thus, the efficacy of an ADC is dependent not only on the presence of cell surface antigens, but also in-tact delivery of the conjugated drug, and an active pathway of receptor-mediated endocytosis. On a cellular level, the biological mechanisms behind receptor internalization and turnover have not been elucidated for novel therapeutic targets. On a tissue level, vascularization and hypoxic profile will affect delivery of the antibody into the tissue. Varying expression of the antibody target within the tissue (antigen density) will also affect the uptake of the ADC. Furthermore, the extracellular stability of the ADC may be affected by the activity of the various proteases in the tumor microenvironment (TME), outside of the lysozome. These concepts are critical for efficacy, and thus are especially important for companion diagnostic approaches (CDx) meant to predict response to ADCs. Thus, a predictive assay which would account not only for the degree of cell surface expression of the target, but also receptor internalization and potential effects of tumor microenvironment is required. To answer this need, Flagship Biosciences has invented several proprietary approaches for measuring critical properties of the therapeutic target on the cell surface or inside the cell, as well as properties of the TME which could be used to understand and predict efficacy to an ADC using FFPE biopsies. These quantitative pathology approaches are based on image analysis approaches which been designed specifically for ADC CDx programs to answer these critical questions: 1) Defining cell surface target expression independent of cytoplasmic expression; 2) Estimating receptor flux (turnover, internalization) based on staining profile; 3) Assessing critical factors in the TME which may affect delivery of the in-tact drug to the intracellular target; 4) Assaying vascular properties which may affect delivery of the drug; and 5) Heterogeneity of the target within a tumor. We are able to provide these as discrete evaluations or multiplex these evaluations for an integrative answer which can be derived from a typical clinical biopsy. Incorporation of these novel tools will enable ADC developers to create efficacy and patient stratification paradigms which incorporate the critical biological endpoints unique to ADCs. Citation Format: Joseph S. Krueger, Holger Lange, Steve Potts, David Young. Assessing factors predictive of response to ADCs for companion diagnostic strategies. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5426. doi:10.1158/1538-7445.AM2014-5426" @default.
• W2073496670 created "2016-06-24" @default.
• W2073496670 creator A5003285094 @default.
• W2073496670 creator A5025121062 @default.
• W2073496670 creator A5056189405 @default.
• W2073496670 creator A5075929261 @default.
• W2073496670 date "2014-09-30" @default.
• W2073496670 modified "2023-09-27" @default.
• W2073496670 title "Abstract 5426: Assessing factors predictive of response to ADCs for companion diagnostic strategies" @default.
• W2073496670 doi "https://doi.org/10.1158/1538-7445.am2014-5426" @default.
• W2073496670 hasPublicationYear "2014" @default.
• W2073496670 type Work @default.
• W2073496670 sameAs 2073496670 @default.
• W2073496670 citedByCount "0" @default.
• W2073496670 crossrefType "proceedings-article" @default.
• W2073496670 hasAuthorship W2073496670A5003285094 @default.
• W2073496670 hasAuthorship W2073496670A5025121062 @default.
• W2073496670 hasAuthorship W2073496670A5056189405 @default.
• W2073496670 hasAuthorship W2073496670A5075929261 @default.
• W2073496670 hasConcept C139770010 @default.
• W2073496670 hasConcept C147483822 @default.
• W2073496670 hasConcept C1491633281 @default.
• W2073496670 hasConcept C159654299 @default.
• W2073496670 hasConcept C181199279 @default.
• W2073496670 hasConcept C182220744 @default.
• W2073496670 hasConcept C185592680 @default.
• W2073496670 hasConcept C203014093 @default.
• W2073496670 hasConcept C2776107976 @default.
• W2073496670 hasConcept C28005876 @default.
• W2073496670 hasConcept C3020616263 @default.
• W2073496670 hasConcept C502942594 @default.
• W2073496670 hasConcept C542903549 @default.
• W2073496670 hasConcept C55493867 @default.
• W2073496670 hasConcept C86803240 @default.
• W2073496670 hasConcept C95444343 @default.
• W2073496670 hasConceptScore W2073496670C139770010 @default.
• W2073496670 hasConceptScore W2073496670C147483822 @default.
• W2073496670 hasConceptScore W2073496670C1491633281 @default.
• W2073496670 hasConceptScore W2073496670C159654299 @default.
• W2073496670 hasConceptScore W2073496670C181199279 @default.
• W2073496670 hasConceptScore W2073496670C182220744 @default.
• W2073496670 hasConceptScore W2073496670C185592680 @default.
• W2073496670 hasConceptScore W2073496670C203014093 @default.
• W2073496670 hasConceptScore W2073496670C2776107976 @default.
• W2073496670 hasConceptScore W2073496670C28005876 @default.
• W2073496670 hasConceptScore W2073496670C3020616263 @default.
• W2073496670 hasConceptScore W2073496670C502942594 @default.
• W2073496670 hasConceptScore W2073496670C542903549 @default.
• W2073496670 hasConceptScore W2073496670C55493867 @default.
• W2073496670 hasConceptScore W2073496670C86803240 @default.
• W2073496670 hasConceptScore W2073496670C95444343 @default.
• W2073496670 hasLocation W20734966701 @default.
• W2073496670 hasOpenAccess W2073496670 @default.
• W2073496670 hasPrimaryLocation W20734966701 @default.
• W2073496670 hasRelatedWork W1491750230 @default.
• W2073496670 hasRelatedWork W1975898060 @default.
• W2073496670 hasRelatedWork W1999560388 @default.
• W2073496670 hasRelatedWork W2178854496 @default.
• W2073496670 hasRelatedWork W2179163778 @default.
• W2073496670 hasRelatedWork W2312797866 @default.
• W2073496670 hasRelatedWork W2399902420 @default.
• W2073496670 hasRelatedWork W2490990783 @default.
• W2073496670 hasRelatedWork W2740718966 @default.
• W2073496670 hasRelatedWork W2774754307 @default.
• W2073496670 hasRelatedWork W2791411921 @default.
• W2073496670 hasRelatedWork W2888228317 @default.
• W2073496670 hasRelatedWork W2892036033 @default.
• W2073496670 hasRelatedWork W2953849350 @default.
• W2073496670 hasRelatedWork W2955072468 @default.
• W2073496670 hasRelatedWork W2992055542 @default.
• W2073496670 hasRelatedWork W3005359701 @default.
• W2073496670 hasRelatedWork W3171020776 @default.
• W2073496670 hasRelatedWork W3196599775 @default.
• W2073496670 hasRelatedWork W3212191448 @default.
• W2073496670 isParatext "false" @default.
• W2073496670 isRetracted "false" @default.
• W2073496670 magId "2073496670" @default.
• W2073496670 workType "article" @default.