Matches in SemOpenAlex for { <https://semopenalex.org/work/W4313383800> ?p ?o ?g. }
Showing items 1 to 70 of
70
with 100 items per page.
- W4313383800 endingPage "58.14" @default.
- W4313383800 startingPage "58.14" @default.
- W4313383800 abstract "Abstract Acquired drug resistance is a longstanding challenge that reduces the efficacy of chemotherapeutic drugs. In contrast, the efficacies of modern immunotherapies do not directly correlate to the prevalence of chemo-resistant phenotypes. Here we improve upon this paradigm by targeting the action of immunotherapeutics to two general mechanisms of acquired drug resistance: irregular metabolism and drug efflux mediated by the ABC superfamily of transport proteins. In chemo-resistant prostate cancer cells, we demonstrate that these two mechanisms act in concert to selectively metabolize our newly developed class of enzyme-directed prodrug to the Toll-Like Receptor 7 immunotherapeutic Imiquimod. Following metabolism, liberated Imiquimod undergoes drug efflux to the extracellular space where it activates bystander immune cells in local proximity. In-vitro, we characterize this process of Bystander-Assisted ImmunoTherapy (BAIT) using an AT3B-1 chemo-resistant prostate cancer model with RAW-Blue and JAWSII reporter immune cell lines. Co-culture of AT3B-1 cancer cells with reporter immune cells results in immunogenicity mediated selectively by cancer cells. This results in enhanced NF-κB transcription, expression of cell surface markers, and secreted cytokines indicative of a cell-mediated immune response. Our prodrug is non-immunogenic with healthy cells alone and the enzyme-directing groups are stable for over 3 days in serum. Taken together, our results demonstrate that BAIT co-opts common mechanisms of drug resistance to elicit immunogenicity mediated by cancer cells themselves. We anticipate that BAIT will find use as a new mechanism of action that exploits drug resistant phenotypes to generate an immune response." @default.
- W4313383800 created "2023-01-06" @default.
- W4313383800 creator A5022659802 @default.
- W4313383800 creator A5024558039 @default.
- W4313383800 creator A5047700344 @default.
- W4313383800 creator A5049841341 @default.
- W4313383800 date "2018-05-01" @default.
- W4313383800 modified "2023-10-16" @default.
- W4313383800 title "Drugging drug resistance with bystander-assisted immunotherapy." @default.
- W4313383800 doi "https://doi.org/10.4049/jimmunol.200.supp.58.14" @default.
- W4313383800 hasPublicationYear "2018" @default.
- W4313383800 type Work @default.
- W4313383800 citedByCount "0" @default.
- W4313383800 crossrefType "journal-article" @default.
- W4313383800 hasAuthorship W4313383800A5022659802 @default.
- W4313383800 hasAuthorship W4313383800A5024558039 @default.
- W4313383800 hasAuthorship W4313383800A5047700344 @default.
- W4313383800 hasAuthorship W4313383800A5049841341 @default.
- W4313383800 hasConcept C108215921 @default.
- W4313383800 hasConcept C114851261 @default.
- W4313383800 hasConcept C121608353 @default.
- W4313383800 hasConcept C19106626 @default.
- W4313383800 hasConcept C203014093 @default.
- W4313383800 hasConcept C2777701055 @default.
- W4313383800 hasConcept C2779112978 @default.
- W4313383800 hasConcept C2780192828 @default.
- W4313383800 hasConcept C2780868878 @default.
- W4313383800 hasConcept C502942594 @default.
- W4313383800 hasConcept C54355233 @default.
- W4313383800 hasConcept C86803240 @default.
- W4313383800 hasConcept C8891405 @default.
- W4313383800 hasConcept C89423630 @default.
- W4313383800 hasConcept C96232424 @default.
- W4313383800 hasConcept C98274493 @default.
- W4313383800 hasConceptScore W4313383800C108215921 @default.
- W4313383800 hasConceptScore W4313383800C114851261 @default.
- W4313383800 hasConceptScore W4313383800C121608353 @default.
- W4313383800 hasConceptScore W4313383800C19106626 @default.
- W4313383800 hasConceptScore W4313383800C203014093 @default.
- W4313383800 hasConceptScore W4313383800C2777701055 @default.
- W4313383800 hasConceptScore W4313383800C2779112978 @default.
- W4313383800 hasConceptScore W4313383800C2780192828 @default.
- W4313383800 hasConceptScore W4313383800C2780868878 @default.
- W4313383800 hasConceptScore W4313383800C502942594 @default.
- W4313383800 hasConceptScore W4313383800C54355233 @default.
- W4313383800 hasConceptScore W4313383800C86803240 @default.
- W4313383800 hasConceptScore W4313383800C8891405 @default.
- W4313383800 hasConceptScore W4313383800C89423630 @default.
- W4313383800 hasConceptScore W4313383800C96232424 @default.
- W4313383800 hasConceptScore W4313383800C98274493 @default.
- W4313383800 hasIssue "1_Supplement" @default.
- W4313383800 hasLocation W43133838001 @default.
- W4313383800 hasOpenAccess W4313383800 @default.
- W4313383800 hasPrimaryLocation W43133838001 @default.
- W4313383800 hasRelatedWork W1565690560 @default.
- W4313383800 hasRelatedWork W1572810235 @default.
- W4313383800 hasRelatedWork W2010057931 @default.
- W4313383800 hasRelatedWork W2071315909 @default.
- W4313383800 hasRelatedWork W2109755328 @default.
- W4313383800 hasRelatedWork W2327043232 @default.
- W4313383800 hasRelatedWork W2411114470 @default.
- W4313383800 hasRelatedWork W3028762050 @default.
- W4313383800 hasRelatedWork W4291367166 @default.
- W4313383800 hasRelatedWork W4360983034 @default.
- W4313383800 hasVolume "200" @default.
- W4313383800 isParatext "false" @default.
- W4313383800 isRetracted "false" @default.
- W4313383800 workType "article" @default.