Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia

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dc.contributor.authorLaborda, Eduardoko
dc.contributor.authorMazagova, Magdalenako
dc.contributor.authorShao, Sidako
dc.contributor.authorWang, Xinxinko
dc.contributor.authorQuirino, Herlindako
dc.contributor.authorWoods, Ashley K.ko
dc.contributor.authorHampton, Eric N.ko
dc.contributor.authorRodgers, David T.ko
dc.contributor.authorKim, Chan Hyukko
dc.contributor.authorSchultz, Peter G.ko
dc.contributor.authorYoung, Travis S.ko
dc.date.accessioned2018-01-22T09:03:04Z-
dc.date.available2018-01-22T09:03:04Z-
dc.date.created2017-11-14-
dc.date.created2017-11-14-
dc.date.issued2017-10-
dc.identifier.citationINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.18, no.11, pp.2259 - 2266-
dc.identifier.issn1422-0067-
dc.identifier.urihttp://hdl.handle.net/10203/237715-
dc.description.abstractThe treatment of patients with acute myeloid leukemia (AML) with targeted immunotherapy is challenged by the heterogeneity of the disease and a lack of tumor-exclusive antigens. Conventional immunotherapy targets for AML such as CD33 and CD123 have been proposed as targets for chimeric antigen receptor (CAR)-engineered T-cells (CAR-T-cells), a therapy that has been highly successful in the treatment of B-cell leukemia and lymphoma. However, CD33 and CD123 are present on hematopoietic stem cells, and targeting with CAR-T-cells has the potential to elicit long-term myelosuppression. C-type lectin-like molecule-1 (CLL1 or CLEC12A) is a myeloid lineage antigen that is expressed by malignant cells in more than 90% of AML patients. CLL1 is not expressed by healthy Hematopoietic Stem Cells (HSCs), and is therefore a promising target for CAR-T-cell therapy. Here, we describe the development and optimization of an anti-CLL1 CAR-T-cell with potent activity on both AML cell lines and primary patient-derived AML blasts in vitro while sparing healthy HSCs. Furthermore, in a disseminated mouse xenograft model using the CLL1-positive HL60 cell line, these CAR-T-cells completely eradicated tumor, thus supporting CLL1 as a promising target for CAR-T-cells to treat AML while limiting myelosuppressive toxicity.-
dc.languageEnglish-
dc.publisherMDPI-
dc.titleDevelopment of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia-
dc.typeArticle-
dc.identifier.wosid000416811300033-
dc.identifier.scopusid2-s2.0-85032588778-
dc.type.rimsART-
dc.citation.volume18-
dc.citation.issue11-
dc.citation.beginningpage2259-
dc.citation.endingpage2266-
dc.citation.publicationnameINTERNATIONAL JOURNAL OF MOLECULAR SCIENCES-
dc.identifier.doi10.3390/ijms18112259-
dc.contributor.localauthorKim, Chan Hyuk-
dc.contributor.nonIdAuthorLaborda, Eduardo-
dc.contributor.nonIdAuthorMazagova, Magdalena-
dc.contributor.nonIdAuthorShao, Sida-
dc.contributor.nonIdAuthorWang, Xinxin-
dc.contributor.nonIdAuthorQuirino, Herlinda-
dc.contributor.nonIdAuthorWoods, Ashley K.-
dc.contributor.nonIdAuthorHampton, Eric N.-
dc.contributor.nonIdAuthorRodgers, David T.-
dc.contributor.nonIdAuthorSchultz, Peter G.-
dc.contributor.nonIdAuthorYoung, Travis S.-
dc.description.isOpenAccessY-
dc.type.journalArticleArticle-
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