دورية أكاديمية
Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia.
العنوان: | Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia. |
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المؤلفون: | Laborda E; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. elaborda@calibr.org., Mazagova M; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. magdalena.mazagova@vrtx.com., Shao S; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 11119, USA. sidashao@scripps.edu., Wang X; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. xwang@poseida.com., Quirino H; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. hquirino@calibr.org., Woods AK; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. awoods@calibr.org., Hampton EN; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. ehampton@calibr.org., Rodgers DT; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. drodgers@regulusrx.com., Kim CH; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. kimchanhyuk@kaist.ac.kr.; Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea. kimchanhyuk@kaist.ac.kr., Schultz PG; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. schultz@scripps.edu.; Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 11119, USA. schultz@scripps.edu., Young TS; Department of Biology, California Institute for Biomedical Research (Calibr), La Jolla, CA 11119, USA. tyoung@calibr.org. |
المصدر: | International journal of molecular sciences [Int J Mol Sci] 2017 Oct 27; Vol. 18 (11). Date of Electronic Publication: 2017 Oct 27. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Basel, Switzerland : MDPI, [2000- |
مواضيع طبية MeSH: | Recombinant Fusion Proteins*, Lectins, C-Type/*antagonists & inhibitors , Leukemia, Myeloid, Acute/*immunology , Leukemia, Myeloid, Acute/*metabolism , Receptors, Antigen, T-Cell/*metabolism , Receptors, Mitogen/*antagonists & inhibitors , T-Lymphocytes/*immunology , T-Lymphocytes/*metabolism, Animals ; Antigens, Neoplasm/immunology ; Cell Line, Tumor ; Cytotoxicity, Immunologic ; Disease Models, Animal ; Female ; Humans ; Immunotherapy, Adoptive/methods ; Lectins, C-Type/immunology ; Leukemia, Myeloid, Acute/genetics ; Leukemia, Myeloid, Acute/therapy ; Mice ; Receptors, Antigen, T-Cell/genetics ; Receptors, Mitogen/immunology ; Single-Chain Antibodies/genetics ; Single-Chain Antibodies/immunology ; Single-Chain Antibodies/metabolism ; Xenograft Model Antitumor Assays |
مستخلص: | The 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. Competing Interests: The authors declare no conflict of interest. |
References: | Stem Cells. 2008 Dec;26(12):3059-67. (PMID: 19096043) Haematologica. 2010 Jan;95(1):71-8. (PMID: 19648166) Angew Chem Int Ed Engl. 2014 Sep 8;53(37):9841-5. (PMID: 25056598) Mol Ther. 2015 Jan;23(1):184-91. (PMID: 25174587) Int J Cancer. 2014 Sep 1;135(5):1178-86. (PMID: 24501019) Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3360-5. (PMID: 19211796) Eur J Immunol. 2013 Mar;43(3):747-57. (PMID: 23175469) Blood. 2014 Apr 10;123(15):2343-54. (PMID: 24596416) J Immunother. 2005 May-Jun;28(3):203-11. (PMID: 15838376) J Immunol. 2001 Nov 15;167(10):6021-30. (PMID: 11698483) Cancer Immunol Res. 2015 Feb;3(2):125-35. (PMID: 25212991) J Leukoc Biol. 2010 Dec;88(6):1163-70. (PMID: 20686115) Clin Cancer Res. 2013 Jun 15;19(12):3153-64. (PMID: 23620405) J Immunol. 2004 Dec 15;173(12):7125-30. (PMID: 15585832) Blood. 2013 Oct 31;122(18):3138-48. (PMID: 24030378) Proc Natl Acad Sci U S A. 2016 Jan 26;113(4):E459-68. (PMID: 26759369) Leukemia. 2014 Aug;28(8):1596-605. (PMID: 24504024) J Clin Invest. 2014 Dec;124(12):5466-80. (PMID: 25384214) Haematologica. 2015 Mar;100(3):336-44. (PMID: 25480499) Mol Ther. 2009 Aug;17(8):1453-64. (PMID: 19384291) Cancer Res. 2004 Nov 15;64(22):8443-50. (PMID: 15548716) Br J Haematol. 2013 May;161(3):389-401. (PMID: 23432359) Blood. 2017 Apr 27;129(17 ):2395-2407. (PMID: 28246194) Mol Ther. 2017 Sep 6;25(9):2202-2213. (PMID: 28676343) Blood. 2013 Aug 1;122(5):749-58. (PMID: 23733335) Blood. 2007 Oct 1;110(7):2659-66. (PMID: 17609428) Support Care Cancer. 2014 Mar;22(3):667-77. (PMID: 24154740) Hum Gene Ther. 2017 Mar;28(3):231-241. (PMID: 27967241) |
فهرسة مساهمة: | Keywords: AML; CAR-T-cell; CLL-1; hematopoiesis; optimization |
المشرفين على المادة: | 0 (Antigens, Neoplasm) 0 (CLEC12A protein, human) 0 (Lectins, C-Type) 0 (Receptors, Antigen, T-Cell) 0 (Receptors, Mitogen) 0 (Recombinant Fusion Proteins) 0 (Single-Chain Antibodies) |
تواريخ الأحداث: | Date Created: 20171028 Date Completed: 20180619 Latest Revision: 20181113 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC5713229 |
DOI: | 10.3390/ijms18112259 |
PMID: | 29077054 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1422-0067 |
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DOI: | 10.3390/ijms18112259 |