FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2596236883> ?p ?o ?g. }

• W2596236883 abstract "Abstract Abstract 950 Current treatment regimes for acute myeloid leukemia (AML) achieve complete remissions in only a subset of individuals and most adult patients will relapse within 5-years, emphasizing the need for novel treatment alternatives. One such therapy may be the administration of T cells engineered to express chimeric antigen receptors (CARs) specific for AML-associated antigens. CARs are typically composed of a single chain variable fragment (scFv) from a monoclonal antibody fused to the CD3ζ signaling domain and may contain one or more costimulatory endodomains. When expressed in T cells, CARs redirect T cell specificity to surface antigens on target cells in an MHC-independent manner. The interleukin 3 receptor alpha chain (IL3Rα, CD123) is a cell surface receptor which is aberrantly over-expressed on multiple hematologic malignancies including AML. Previous work has demonstrated that CD123 is not expressed on all CD34+/CD38− hematopoietic stem cells and is restricted to cells of the myeloid lineage, making CD123 an attractive target for CAR T cell therapy. We have therefore generated two novel CD123-specific (CD123R) CARs using scFvs from previously characterized antibodies, designated 26292 and 32716, which bind two distinct epitopes on CD123. Here we demonstrate that T cells expressing CARs derived from either 26292 or 32716 effectively redirect T cell specificity against CD123+ cells. Healthy donor T cells (n=3) engineered to express the CD123R CARs efficiently lysed CD123+ cell lines LCL and KG1a while sparing the CD123− cell line K562 as demonstrated by a 4 hour chromium-51 (51Cr) release assay. Additionally, both of the CD123R CAR T cells produced similar levels of IFN-γ and TNF-α and displayed comparable levels of antigen-dependent proliferation following co-culture with CD123+ cell lines. The potent cytolytic activity and activation of our CD123-targeting T cells was not limited to tumor cell lines. Indeed, CD123R CAR T cells, but not donor-matched CD19-specific (CD19R) CAR T cells, robustly lysed panel of primary AML samples (n=6, 3 – persistent, 1 – relapsed, 2 - untreated) (* p<0.05, ** p<0.001 using the unpaired students' t-test comparing 26292 or 32716 CAR T cells to donor-matched CD19R CAR T cells), and exhibited multiple effector functions for both CD4 and CD8 T cell subsets (ie CD107a degranulation, IFN-γ and TNF-α production, and antigen specific proliferation) when co-cultured with primary AML samples (n=3, 2 – relapsed, 1-persistent). To examine the effect our CD123-specific T cells have on normal and leukemic progenitor cells, we co-cultured CD123R CAR T cells, or donor-matched CD19-targeting T cells, with either CD34-enriched cord blood (CB, n=3) or primary AML samples (n=3, 2 – relapsed, 1 - untreated) for 4 hours (E:T 25:1) prior to plating in semisolid methylcellulose progenitor culture. CD123-targeting T cells did not significantly reduce the number of colony-forming unit granulocyte-macrophage (CFU-GM) or burst-forming unit erythroid (BFU-E) colonies from CB when compared to CD19R CAR T cells. Finally, while CD19-specific T cells had little impact on leukemic colony formation of primary AML samples, CD123-targeting T cells significantly reduced leukemic colony formation in vitro. Collectively, our data demonstrate that CD123-specifc CARs can be expressed in primary healthy donor T cells, distinguish between CD123+ and CD123− cells, and mediate robust anti-leukemic activity against a panel of poor-risk primary AML patient samples. Importantly, we demonstrate that CD123R CAR T cells have little impact on normal progenitor colony formation while significantly reducing the growth of clonogenic myeloid leukemic progentiors in vitro. Thus, CD123R CAR T cells are a promising candidate for future immunotherapy of AML. Disclosures: Bhatia: Novartis: Consultancy, Honoraria. Jensen:ZetaRx: Equity Ownership, Patents & Royalties." @default.
• W2596236883 created "2017-03-23" @default.
• W2596236883 creator A5003368238 @default.
• W2596236883 creator A5006737562 @default.
• W2596236883 creator A5010868067 @default.
• W2596236883 creator A5010964073 @default.
• W2596236883 creator A5011178245 @default.
• W2596236883 creator A5028928234 @default.
• W2596236883 creator A5031641921 @default.
• W2596236883 creator A5032663202 @default.
• W2596236883 creator A5039374832 @default.
• W2596236883 creator A5075158998 @default.
• W2596236883 date "2012-11-16" @default.
• W2596236883 modified "2023-09-30" @default.
• W2596236883 title "CD123-Specific Chimeric Antigen Receptor Redirected T Cells Exhibit Potent Cytolytic Activity and Multiple Effector Functions Against Acute Myeloid Leukemia without Altering Normal Hematopoietic Colony Formation in Vitro" @default.
• W2596236883 doi "https://doi.org/10.1182/blood.v120.21.950.950" @default.
• W2596236883 hasPublicationYear "2012" @default.
• W2596236883 type Work @default.
• W2596236883 sameAs 2596236883 @default.
• W2596236883 citedByCount "1" @default.
• W2596236883 countsByYear W25962368832013 @default.
• W2596236883 crossrefType "journal-article" @default.
• W2596236883 hasAuthorship W2596236883A5003368238 @default.
• W2596236883 hasAuthorship W2596236883A5006737562 @default.
• W2596236883 hasAuthorship W2596236883A5010868067 @default.
• W2596236883 hasAuthorship W2596236883A5010964073 @default.
• W2596236883 hasAuthorship W2596236883A5011178245 @default.
• W2596236883 hasAuthorship W2596236883A5028928234 @default.
• W2596236883 hasAuthorship W2596236883A5031641921 @default.
• W2596236883 hasAuthorship W2596236883A5032663202 @default.
• W2596236883 hasAuthorship W2596236883A5039374832 @default.
• W2596236883 hasAuthorship W2596236883A5075158998 @default.
• W2596236883 hasConcept C109159458 @default.
• W2596236883 hasConcept C147483822 @default.
• W2596236883 hasConcept C203014093 @default.
• W2596236883 hasConcept C2776090121 @default.
• W2596236883 hasConcept C2778461978 @default.
• W2596236883 hasConcept C2778729363 @default.
• W2596236883 hasConcept C28328180 @default.
• W2596236883 hasConcept C3875195 @default.
• W2596236883 hasConcept C502942594 @default.
• W2596236883 hasConcept C54355233 @default.
• W2596236883 hasConcept C552990157 @default.
• W2596236883 hasConcept C81089528 @default.
• W2596236883 hasConcept C83396363 @default.
• W2596236883 hasConcept C86803240 @default.
• W2596236883 hasConcept C8891405 @default.
• W2596236883 hasConcept C95444343 @default.
• W2596236883 hasConceptScore W2596236883C109159458 @default.
• W2596236883 hasConceptScore W2596236883C147483822 @default.
• W2596236883 hasConceptScore W2596236883C203014093 @default.
• W2596236883 hasConceptScore W2596236883C2776090121 @default.
• W2596236883 hasConceptScore W2596236883C2778461978 @default.
• W2596236883 hasConceptScore W2596236883C2778729363 @default.
• W2596236883 hasConceptScore W2596236883C28328180 @default.
• W2596236883 hasConceptScore W2596236883C3875195 @default.
• W2596236883 hasConceptScore W2596236883C502942594 @default.
• W2596236883 hasConceptScore W2596236883C54355233 @default.
• W2596236883 hasConceptScore W2596236883C552990157 @default.
• W2596236883 hasConceptScore W2596236883C81089528 @default.
• W2596236883 hasConceptScore W2596236883C83396363 @default.
• W2596236883 hasConceptScore W2596236883C86803240 @default.
• W2596236883 hasConceptScore W2596236883C8891405 @default.
• W2596236883 hasConceptScore W2596236883C95444343 @default.
• W2596236883 hasLocation W25962368831 @default.
• W2596236883 hasOpenAccess W2596236883 @default.
• W2596236883 hasPrimaryLocation W25962368831 @default.
• W2596236883 hasRelatedWork W2052597485 @default.
• W2596236883 hasRelatedWork W2342739707 @default.
• W2596236883 hasRelatedWork W2471233625 @default.
• W2596236883 hasRelatedWork W2512142474 @default.
• W2596236883 hasRelatedWork W2524091414 @default.
• W2596236883 hasRelatedWork W2537116314 @default.
• W2596236883 hasRelatedWork W2560899846 @default.
• W2596236883 hasRelatedWork W2564307027 @default.
• W2596236883 hasRelatedWork W2566868731 @default.
• W2596236883 hasRelatedWork W2575016736 @default.
• W2596236883 hasRelatedWork W2613098363 @default.
• W2596236883 hasRelatedWork W2613167619 @default.
• W2596236883 hasRelatedWork W2890084495 @default.
• W2596236883 hasRelatedWork W2914877161 @default.
• W2596236883 hasRelatedWork W2966514455 @default.
• W2596236883 hasRelatedWork W2979737548 @default.
• W2596236883 hasRelatedWork W2980264439 @default.
• W2596236883 hasRelatedWork W3033918043 @default.
• W2596236883 hasRelatedWork W3095774471 @default.
• W2596236883 hasRelatedWork W3133647656 @default.
• W2596236883 isParatext "false" @default.
• W2596236883 isRetracted "false" @default.
• W2596236883 magId "2596236883" @default.
• W2596236883 workType "article" @default.