دورية أكاديمية
CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response.
| العنوان: | CD40 Ligand-Modified Chimeric Antigen Receptor T Cells Enhance Antitumor Function by Eliciting an Endogenous Antitumor Response. |
|---|---|
| المؤلفون: | Kuhn NF; Louis V. Gerstner Jr. Graduate School of Biomedical Sciences, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Purdon TJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., van Leeuwen DG; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Lopez AV; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Curran KJ; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Daniyan AF; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Brentjens RJ; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: brentjer@mskcc.org. |
| المصدر: | Cancer cell [Cancer Cell] 2019 Mar 18; Vol. 35 (3), pp. 473-488.e6. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101130617 Publication Model: Print Cited Medium: Internet ISSN: 1878-3686 (Electronic) Linking ISSN: 15356108 NLM ISO Abbreviation: Cancer Cell Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Cambridge, Mass. : Cell Press, c2002- |
| مواضيع طبية MeSH: | CD40 Ligand/*immunology , Immunotherapy, Adoptive/*methods , Neoplasms/*therapy , Receptors, Chimeric Antigen/*immunology, Animals ; Antigen-Presenting Cells/immunology ; CD40 Ligand/genetics ; Cell Line, Tumor ; Humans ; Mice ; Mice, Inbred BALB C ; Neoplasms/immunology ; Receptors, Chimeric Antigen/genetics ; Tumor Escape ; Xenograft Model Antitumor Assays |
| مستخلص: | Chimeric antigen receptor (CAR) T cells provide great efficacy in B cell malignancies. However, improved CAR T cell therapies are still needed. Here, we engineered tumor-targeted CAR T cells to constitutively express the immune-stimulatory molecule CD40 ligand (CD40L) and explored efficacy in different mouse leukemia/lymphoma models. We observed that CD40L + CAR T cells circumvent tumor immune escape via antigen loss through CD40/CD40L-mediated cytotoxicity and induction of a sustained, endogenous immune response. After adoptive cell transfer, the CD40L + CAR T cells displayed superior antitumor efficacy, licensed antigen-presenting cells, enhanced recruitment of immune effectors, and mobilized endogenous tumor-recognizing T cells. These effects were absent in Cd40 -/- mice and provide a rationale for the use of CD40L + CAR T cells in cancer treatment. (Copyright © 2019 Elsevier Inc. All rights reserved.) |
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| معلومات مُعتمدة: | R01 CA138738 United States CA NCI NIH HHS; F31 CA213668 United States CA NCI NIH HHS; P50 CA192937 United States CA NCI NIH HHS; P30 CA008748 United States CA NCI NIH HHS; P01 CA190174 United States CA NCI NIH HHS; P01 CA059350 United States CA NCI NIH HHS; K12 CA184746 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: CAR T cells; CD40; CD40 ligand; antigen-presenting cells; chimeric antigen receptor; endogenous T cells; immunotherapy; leukemia; lymphoma |
| المشرفين على المادة: | 0 (Receptors, Chimeric Antigen) 147205-72-9 (CD40 Ligand) |
| تواريخ الأحداث: | Date Created: 20190320 Date Completed: 20191223 Latest Revision: 20210617 |
| رمز التحديث: | 20240628 |
| مُعرف محوري في PubMed: | PMC6428219 |
| DOI: | 10.1016/j.ccell.2019.02.006 |
| PMID: | 30889381 |
| قاعدة البيانات: | MEDLINE |
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