Article ; Online: TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.
2024 Volume 15, Issue 1, Page(s) 3882
Abstract: In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade ... ...
| Abstract | In this randomized phase II clinical trial, we evaluated the effectiveness of adding the TLR agonists, poly-ICLC or resiquimod, to autologous tumor lysate-pulsed dendritic cell (ATL-DC) vaccination in patients with newly-diagnosed or recurrent WHO Grade III-IV malignant gliomas. The primary endpoints were to assess the most effective combination of vaccine and adjuvant in order to enhance the immune potency, along with safety. The combination of ATL-DC vaccination and TLR agonist was safe and found to enhance systemic immune responses, as indicated by increased interferon gene expression and changes in immune cell activation. Specifically, PD-1 expression increases on CD4+ T-cells, while CD38 and CD39 expression are reduced on CD8+ T cells, alongside an increase in monocytes. Poly-ICLC treatment amplifies the induction of interferon-induced genes in monocytes and T lymphocytes. Patients that exhibit higher interferon response gene expression demonstrate prolonged survival and delayed disease progression. These findings suggest that combining ATL-DC with poly-ICLC can induce a polarized interferon response in circulating monocytes and CD8+ T cells, which may represent an important blood biomarker for immunotherapy in this patient population.Trial Registration: ClinicalTrials.gov Identifier: NCT01204684. |
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| MeSH term(s) | Humans ; Dendritic Cells/immunology ; Dendritic Cells/drug effects ; Glioma/immunology ; Glioma/therapy ; Female ; Male ; Interferons ; Middle Aged ; Cancer Vaccines/immunology ; Cancer Vaccines/administration & dosage ; Cancer Vaccines/therapeutic use ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/drug effects ; Poly I-C/administration & dosage ; Poly I-C/pharmacology ; Adult ; Toll-Like Receptors/agonists ; Imidazoles/pharmacology ; Imidazoles/therapeutic use ; Aged ; Vaccination ; Monocytes/immunology ; Monocytes/drug effects ; Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Brain Neoplasms/drug therapy ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/drug effects ; Immunotherapy/methods ; Toll-Like Receptor Agonists ; Carboxymethylcellulose Sodium/analogs & derivatives ; Polylysine/analogs & derivatives |
| Chemical Substances | poly ICLC (7KYP9TKT70) ; Interferons (9008-11-1) ; Cancer Vaccines ; Poly I-C (O84C90HH2L) ; resiquimod (V3DMU7PVXF) ; Toll-Like Receptors ; Imidazoles ; Toll-Like Receptor Agonists ; Carboxymethylcellulose Sodium (K679OBS311) ; Polylysine (25104-18-1) |
| Language | English |
| Publishing date | 2024-05-08 |
| Publishing country | England |
| Document type | Journal Article ; Clinical Trial, Phase II ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2553671-0 |
| ISSN | 2041-1723 ; 2041-1723 |
| ISSN (online) | 2041-1723 |
| ISSN | 2041-1723 |
| DOI | 10.1038/s41467-024-48073-y |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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