دورية أكاديمية
أعرض في EDS

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

التفاصيل البيبلوغرافية
العنوان: Development of A Chimeric Antigen Receptor Targeting C-Type Lectin-Like Molecule-1 for Human Acute Myeloid Leukemia.
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.
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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
الوصف
تدمد:1422-0067
DOI:10.3390/ijms18112259