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TLR agonists polarize interferon responses in conjunction with dendritic cell vaccination in malignant glioma: a randomized phase II Trial.
Everson, Richard G; Hugo, Willy; Sun, Lu; Antonios, Joseph; Lee, Alexander; Ding, Lizhong; Bu, Melissa; Khattab, Sara; Chavez, Carolina; Billingslea-Yoon, Emma; Salazar, Andres; Ellingson, Benjamin M; Cloughesy, Timothy F; Liau, Linda M; Prins, Robert M.
Afiliação
  • Everson RG; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Hugo W; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Sun L; Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Antonios J; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Lee A; Parker Institute for Cancer Immunotherapy, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Ding L; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Bu M; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Khattab S; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Chavez C; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Billingslea-Yoon E; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Salazar A; Department of Medicine, Division of Dermatology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Ellingson BM; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Cloughesy TF; Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Liau LM; Department of Neurosurgery, David Geffen School of Medicine at UCLA, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Prins RM; Oncovir, Inc., Winchester, VA, USA.
Nat Commun ; 15(1): 3882, 2024 May 08.
Article em En | MEDLINE | ID: mdl-38719809
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Interferons / Vacinas Anticâncer / Glioma / Agonistas do Receptor Semelhante a Toll Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células Dendríticas / Interferons / Vacinas Anticâncer / Glioma / Agonistas do Receptor Semelhante a Toll Limite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Ano de publicação: 2024 Tipo de documento: Article