دورية أكاديمية
TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1.
| العنوان: | TCR-based therapy for multiple myeloma and other B-cell malignancies targeting intracellular transcription factor BOB1. |
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| المؤلفون: | Jahn L; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Hombrink P; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.; Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands., Hagedoorn RS; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Kester MG; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., van der Steen DM; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Rodriguez T; Research and Development, Bellicum Pharmaceuticals, Inc., Houston, TX., Pentcheva-Hoang T; Research and Development, Bellicum Pharmaceuticals, Inc., Houston, TX., de Ru AH; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Schoonakker MP; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Meeuwsen MH; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Griffioen M; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., van Veelen PA; Center for Proteomics and Metabolomics, Leiden University Medical Center, Leiden, The Netherlands., Falkenburg JH; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands., Heemskerk MH; Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands. |
| المصدر: | Blood [Blood] 2017 Mar 09; Vol. 129 (10), pp. 1284-1295. Date of Electronic Publication: 2017 Jan 04. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Country of Publication: United States NLM ID: 7603509 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1528-0020 (Electronic) Linking ISSN: 00064971 NLM ISO Abbreviation: Blood Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York] : Elsevier Original Publication: New York, Grune & Stratton [etc.] |
| مواضيع طبية MeSH: | Immunotherapy, Adoptive/*methods , Lymphoma, Non-Hodgkin/*immunology , Multiple Myeloma/*immunology , Receptors, Antigen, T-Cell/*immunology , Trans-Activators/*antagonists & inhibitors, Animals ; Cell Line, Tumor ; Flow Cytometry ; Genetic Engineering/methods ; Humans ; Mice ; T-Lymphocytes/immunology ; Xenograft Model Antitumor Assays |
| مستخلص: | Immunotherapy for hematological malignancies or solid tumors by administration of monoclonal antibodies or T cells engineered to express chimeric antigen receptors or T-cell receptors (TCRs) has demonstrated clinical efficacy. However, antigen-loss tumor escape variants and the absence of currently targeted antigens on several malignancies hamper the widespread application of immunotherapy. We have isolated a TCR targeting a peptide of the intracellular B cell-specific transcription factor BOB1 presented in the context of HLA-B*07:02. TCR gene transfer installed BOB1 specificity and reactivity onto recipient T cells. TCR-transduced T cells efficiently lysed primary B-cell leukemia, mantle cell lymphoma, and multiple myeloma in vitro. We also observed recognition and lysis of healthy BOB1-expressing B cells. In addition, strong BOB1-specific proliferation could be demonstrated for TCR-modified T cells upon antigen encounter. Furthermore, clear in vivo antitumor reactivity was observed of BOB1-specific TCR-engineered T cells in a xenograft mouse model of established multiple myeloma. Absence of reactivity toward a broad panel of BOB1 - but HLA-B*07:02 + nonhematopoietic and hematopoietic cells indicated no off-target toxicity. Therefore, administration of BOB1-specific TCR-engineered T cells may provide novel cellular treatment options to patients with B-cell malignancies, including multiple myeloma. (© 2017 by The American Society of Hematology.) |
| التعليقات: | Comment in: Blood. 2017 Mar 9;129(10 ):1236-1237. (PMID: 28280042) |
| المشرفين على المادة: | 0 (POU2AF1 protein, human) 0 (Receptors, Antigen, T-Cell) 0 (Trans-Activators) |
| تواريخ الأحداث: | Date Created: 20170106 Date Completed: 20170814 Latest Revision: 20210202 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1182/blood-2016-09-737536 |
| PMID: | 28053195 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1528-0020 |
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| DOI: | 10.1182/blood-2016-09-737536 |