FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1569677760> ?p ?o ?g. }

• W1569677760 abstract "With the successes of Kadcyla and Adcetris, and the emerging data from early phase trials of many other ADCs our understanding of the critical attributes for target selection and ADC development has improved significantly. Clinical experience indicates that the dose-limiting toxicities observed are predominately off-target and thus are similar across ADCs using the same linker and drug combinations and independent of the target antigen. Furthermore, the maximum tolerated doses (MTDs) in humans, monkeys, and mice for many ADCs seem to be very similar regardless of the protein being targeted. Thus, the therapeutic index of new ADCs using the current drug/linker technologies (tubulin and DNA targeting toxins) will be driven predominately by efficacy, specifically the ability to achieve antitumor activity at exposure levels below the MTD. Therefore, the focus of future target selection should be on efficacy within the therapeutic window rather than on antigen-dependent (i.e. on-target) toxicity arising from normal tissue expression. We have selected targets and toxins for ADC development based on the likelihood of robust potency against cancer cells. The properties favored are : 1) high expression and high prevalence in selected malignancies, 2) normal tissue expression profiles known to be tolerable for ADCs ( e.g. her2neu, gpnmb, nectin4), 3) targets enabling rapid intracellular delivery of ADC and release of active toxin, 4) clinical indications sensitive to the toxin of choice. This process and its success are demonstrated here through the development of two ADCs. Firstly, Ox-1476 for triple negative breast cancer (TNBC). The target was selected based on consistent high expression in TNBC, the MAb selected from a large screen of greater than 1000 candidates based on activity as an actual ADC, and the toxin selected based on the positive experience with maytansine in breast cancer (Kadcyla) and the preclinical data presented here. The Ox-1476 ADC shows greater and broader activity than Kadcyla in vitro and an initial toxicity profile consistent with pursuing clinical development. Secondly, Ox-1425 is being developed for small cell lung cancer (SCLC). The target and MAb were selected by the same processes but for Ox-1425 the toxin screen resulted in the selection of a DNA alkylating agent. Our proteomics database has provided a unique data set of candidate cell surface targets for the development of antibodies compatible with the current state of the art ADC payloads. The selected targets show high and prevalent expression in cancers, are in protein families shown to internalize efficiently, and have normal tissue expression profiles similar to other proteins already being targeted by clinical stage ADCs. The preclinical safety and activity data shown here is supportive of our strategy for selecting ADC targets. Citation Format: Jonathan A. Terrett, Rachel Dusek, Dee Aud, Rahel Awdew, Sudha Swaminathan, San Lin Lou, Michael Trang, Arnima Bisht, Mary Do, Jim Ackroyd, Robert Boyd, Lindsey Hudson, Phuoc Pham, Nickolas Attanasio, Ami Antani, Carmel Lynch, Christian Rohlff. Proteomics and selecting the right combination of target and toxin for antibody-drug-conjugate (ADC) development. [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 661. doi:10.1158/1538-7445.AM2014-661" @default.
• W1569677760 created "2016-06-24" @default.
• W1569677760 creator A5000579386 @default.
• W1569677760 creator A5002408732 @default.
• W1569677760 creator A5009970073 @default.
• W1569677760 creator A5011861850 @default.
• W1569677760 creator A5019756202 @default.
• W1569677760 creator A5023088864 @default.
• W1569677760 creator A5028886132 @default.
• W1569677760 creator A5039075789 @default.
• W1569677760 creator A5049725402 @default.
• W1569677760 creator A5063620350 @default.
• W1569677760 creator A5063672026 @default.
• W1569677760 creator A5067897497 @default.
• W1569677760 creator A5069023418 @default.
• W1569677760 creator A5079556448 @default.
• W1569677760 creator A5079563585 @default.
• W1569677760 creator A5081251776 @default.
• W1569677760 creator A5089556228 @default.
• W1569677760 date "2014-09-30" @default.
• W1569677760 modified "2023-09-27" @default.
• W1569677760 title "Abstract 661: Proteomics and selecting the right combination of target and toxin for antibody-drug-conjugate (ADC) development" @default.
• W1569677760 doi "https://doi.org/10.1158/1538-7445.am2014-661" @default.
• W1569677760 hasPublicationYear "2014" @default.
• W1569677760 type Work @default.
• W1569677760 sameAs 1569677760 @default.
• W1569677760 citedByCount "0" @default.
• W1569677760 crossrefType "proceedings-article" @default.
• W1569677760 hasAuthorship W1569677760A5000579386 @default.
• W1569677760 hasAuthorship W1569677760A5002408732 @default.
• W1569677760 hasAuthorship W1569677760A5009970073 @default.
• W1569677760 hasAuthorship W1569677760A5011861850 @default.
• W1569677760 hasAuthorship W1569677760A5019756202 @default.
• W1569677760 hasAuthorship W1569677760A5023088864 @default.
• W1569677760 hasAuthorship W1569677760A5028886132 @default.
• W1569677760 hasAuthorship W1569677760A5039075789 @default.
• W1569677760 hasAuthorship W1569677760A5049725402 @default.
• W1569677760 hasAuthorship W1569677760A5063620350 @default.
• W1569677760 hasAuthorship W1569677760A5063672026 @default.
• W1569677760 hasAuthorship W1569677760A5067897497 @default.
• W1569677760 hasAuthorship W1569677760A5069023418 @default.
• W1569677760 hasAuthorship W1569677760A5079556448 @default.
• W1569677760 hasAuthorship W1569677760A5079563585 @default.
• W1569677760 hasAuthorship W1569677760A5081251776 @default.
• W1569677760 hasAuthorship W1569677760A5089556228 @default.
• W1569677760 hasConcept C111919701 @default.
• W1569677760 hasConcept C121608353 @default.
• W1569677760 hasConcept C126322002 @default.
• W1569677760 hasConcept C159654299 @default.
• W1569677760 hasConcept C19831878 @default.
• W1569677760 hasConcept C203014093 @default.
• W1569677760 hasConcept C2777325958 @default.
• W1569677760 hasConcept C2780035454 @default.
• W1569677760 hasConcept C2780557392 @default.
• W1569677760 hasConcept C41008148 @default.
• W1569677760 hasConcept C502942594 @default.
• W1569677760 hasConcept C542903549 @default.
• W1569677760 hasConcept C64903051 @default.
• W1569677760 hasConcept C70721500 @default.
• W1569677760 hasConcept C71924100 @default.
• W1569677760 hasConcept C86803240 @default.
• W1569677760 hasConcept C98274493 @default.
• W1569677760 hasConceptScore W1569677760C111919701 @default.
• W1569677760 hasConceptScore W1569677760C121608353 @default.
• W1569677760 hasConceptScore W1569677760C126322002 @default.
• W1569677760 hasConceptScore W1569677760C159654299 @default.
• W1569677760 hasConceptScore W1569677760C19831878 @default.
• W1569677760 hasConceptScore W1569677760C203014093 @default.
• W1569677760 hasConceptScore W1569677760C2777325958 @default.
• W1569677760 hasConceptScore W1569677760C2780035454 @default.
• W1569677760 hasConceptScore W1569677760C2780557392 @default.
• W1569677760 hasConceptScore W1569677760C41008148 @default.
• W1569677760 hasConceptScore W1569677760C502942594 @default.
• W1569677760 hasConceptScore W1569677760C542903549 @default.
• W1569677760 hasConceptScore W1569677760C64903051 @default.
• W1569677760 hasConceptScore W1569677760C70721500 @default.
• W1569677760 hasConceptScore W1569677760C71924100 @default.
• W1569677760 hasConceptScore W1569677760C86803240 @default.
• W1569677760 hasConceptScore W1569677760C98274493 @default.
• W1569677760 hasLocation W15696777601 @default.
• W1569677760 hasOpenAccess W1569677760 @default.
• W1569677760 hasPrimaryLocation W15696777601 @default.
• W1569677760 hasRelatedWork W1905936601 @default.
• W1569677760 hasRelatedWork W2007756994 @default.
• W1569677760 hasRelatedWork W2028791057 @default.
• W1569677760 hasRelatedWork W2054679149 @default.
• W1569677760 hasRelatedWork W2063044400 @default.
• W1569677760 hasRelatedWork W2091368548 @default.
• W1569677760 hasRelatedWork W2172966048 @default.
• W1569677760 hasRelatedWork W2248346391 @default.
• W1569677760 hasRelatedWork W2603088210 @default.
• W1569677760 hasRelatedWork W2605310352 @default.
• W1569677760 hasRelatedWork W2734283637 @default.
• W1569677760 hasRelatedWork W2741195625 @default.
• W1569677760 hasRelatedWork W2800788936 @default.
• W1569677760 hasRelatedWork W2889370697 @default.
• W1569677760 hasRelatedWork W2940945106 @default.
• W1569677760 hasRelatedWork W2950613960 @default.
• W1569677760 hasRelatedWork W2989992836 @default.
• W1569677760 hasRelatedWork W3000428852 @default.

• next