FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2014372297> ?p ?o ?g. }

• W2014372297 endingPage "589" @default.
• W2014372297 startingPage "583" @default.
• W2014372297 abstract "The development of the anti-CTLA-4 antibody (ipilimumab; marketed as Yervoy) immune regulatory therapy was based on the premise that Abrogation of the function of CTLA-4 would permit CD28 to function unopposed and might swing the balance in favor of immune stimulation, tolerance breakdown and tumor eradication… (Weber, 2009). By now, the vast majority of data collected from more than 4000 patients proves that this prediction was entirely correct. Paradoxically, the successful blockade of immune checkpoints raises the question whether an anti-CTLA-4 antibody could ever become an important therapy against cancer. T cells lost their ability to discriminate between self and non-self. Thus, tolerance to self tissues was broken in ∼70% of the patients. In the recent industry-sponsored phase III clinical trial of ipilimumab, 147 (38.7%) of the patients experienced severe adverse events and 6.8% suffered dose-limiting events (8.4%, in the ipilimumab-alone group). There were 14 deaths related to the study drugs and 7 of these were associated with immune-related adverse events. In contrast, the complete response rate was only 0.2%, in one patient out of 403 who received ipilimumab plus a peptide vaccine. Promoters of ipilimumab appear to be unmindful of the clinical trial catastrophe in London. Then, a humanized superagonist anti-CD28 monoclonal antibody, TGN1412, which preferentially activated regulatory T cells, at a higher dose, also activated all CD28 positive T cells. This precipitated a cytokine storm leading to life-threatening multiple organ failure in the six healthy human volunteers. Neither anti-CD28 nor anti-CTLA-4 therapies rely on antigen-specificity. Both release free antibody into the body against common molecular targets that are expressed on the targeted as well as on the non-targeted T cells. At lower antibody doses specific T cells are preferentially activated. With increasing antibody dose, however, the kinetics of the interaction is pushed in favor of widespread non-specific T cell expansion. Using the law of mass action we calculated that the vast majority of the CTLA-4 receptors on all activated T cells (including melanoma specific T cells) in the phase III clinical trial of ipilimumab will have been saturated. This would explain the runaway immune response observed. The conclusions drawn by the authors of the ipilimumab trial paper could bear an independent inspection and reassessment concerning the validation of the blockade of immune checkpoints as an important therapeutic strategy against cancer." @default.
• W2014372297 created "2016-06-24" @default.
• W2014372297 creator A5038949664 @default.
• W2014372297 creator A5040702576 @default.
• W2014372297 creator A5066383247 @default.
• W2014372297 date "2012-06-01" @default.
• W2014372297 modified "2023-09-25" @default.
• W2014372297 title "Ipilimumab (Yervoy) and the TGN1412 catastrophe" @default.
• W2014372297 cites W1536480181 @default.
• W2014372297 cites W1552674833 @default.
• W2014372297 cites W1578975477 @default.
• W2014372297 cites W1617854122 @default.
• W2014372297 cites W2015085911 @default.
• W2014372297 cites W2043455915 @default.
• W2014372297 cites W2045160459 @default.
• W2014372297 cites W2045932062 @default.
• W2014372297 cites W2048091645 @default.
• W2014372297 cites W2053138569 @default.
• W2014372297 cites W2060310993 @default.
• W2014372297 cites W2061071534 @default.
• W2014372297 cites W2063024896 @default.
• W2014372297 cites W2063136099 @default.
• W2014372297 cites W2070266961 @default.
• W2014372297 cites W2076067786 @default.
• W2014372297 cites W2077711565 @default.
• W2014372297 cites W2087013294 @default.
• W2014372297 cites W2087482409 @default.
• W2014372297 cites W2093735344 @default.
• W2014372297 cites W2095826876 @default.
• W2014372297 cites W2097995306 @default.
• W2014372297 cites W2098882304 @default.
• W2014372297 cites W2102143045 @default.
• W2014372297 cites W2110440135 @default.
• W2014372297 cites W2110599247 @default.
• W2014372297 cites W2123264723 @default.
• W2014372297 cites W2130562921 @default.
• W2014372297 cites W2130822830 @default.
• W2014372297 cites W2133649859 @default.
• W2014372297 cites W2139191751 @default.
• W2014372297 cites W2141989396 @default.
• W2014372297 cites W2145308813 @default.
• W2014372297 cites W2146194729 @default.
• W2014372297 cites W2146283287 @default.
• W2014372297 cites W2148576689 @default.
• W2014372297 cites W2150678612 @default.
• W2014372297 cites W2151507811 @default.
• W2014372297 cites W2165335733 @default.
• W2014372297 cites W2168334855 @default.
• W2014372297 cites W2172960056 @default.
• W2014372297 doi "https://doi.org/10.1016/j.imbio.2011.07.005" @default.
• W2014372297 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21821307" @default.
• W2014372297 hasPublicationYear "2012" @default.
• W2014372297 type Work @default.
• W2014372297 sameAs 2014372297 @default.
• W2014372297 citedByCount "35" @default.
• W2014372297 countsByYear W20143722972012 @default.
• W2014372297 countsByYear W20143722972013 @default.
• W2014372297 countsByYear W20143722972014 @default.
• W2014372297 countsByYear W20143722972015 @default.
• W2014372297 countsByYear W20143722972016 @default.
• W2014372297 countsByYear W20143722972017 @default.
• W2014372297 countsByYear W20143722972018 @default.
• W2014372297 countsByYear W20143722972019 @default.
• W2014372297 countsByYear W20143722972020 @default.
• W2014372297 countsByYear W20143722972021 @default.
• W2014372297 countsByYear W20143722972022 @default.
• W2014372297 countsByYear W20143722972023 @default.
• W2014372297 crossrefType "journal-article" @default.
• W2014372297 hasAuthorship W2014372297A5038949664 @default.
• W2014372297 hasAuthorship W2014372297A5040702576 @default.
• W2014372297 hasAuthorship W2014372297A5066383247 @default.
• W2014372297 hasConcept C126322002 @default.
• W2014372297 hasConcept C143998085 @default.
• W2014372297 hasConcept C148125776 @default.
• W2014372297 hasConcept C159654299 @default.
• W2014372297 hasConcept C170493617 @default.
• W2014372297 hasConcept C197934379 @default.
• W2014372297 hasConcept C203014093 @default.
• W2014372297 hasConcept C21705690 @default.
• W2014372297 hasConcept C2776090121 @default.
• W2014372297 hasConcept C2776364478 @default.
• W2014372297 hasConcept C2777701055 @default.
• W2014372297 hasConcept C2778468042 @default.
• W2014372297 hasConcept C2781433595 @default.
• W2014372297 hasConcept C542903549 @default.
• W2014372297 hasConcept C71924100 @default.
• W2014372297 hasConcept C8891405 @default.
• W2014372297 hasConceptScore W2014372297C126322002 @default.
• W2014372297 hasConceptScore W2014372297C143998085 @default.
• W2014372297 hasConceptScore W2014372297C148125776 @default.
• W2014372297 hasConceptScore W2014372297C159654299 @default.
• W2014372297 hasConceptScore W2014372297C170493617 @default.
• W2014372297 hasConceptScore W2014372297C197934379 @default.
• W2014372297 hasConceptScore W2014372297C203014093 @default.
• W2014372297 hasConceptScore W2014372297C21705690 @default.
• W2014372297 hasConceptScore W2014372297C2776090121 @default.
• W2014372297 hasConceptScore W2014372297C2776364478 @default.
• W2014372297 hasConceptScore W2014372297C2777701055 @default.

• next