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Leveraging Endogenous Dendritic Cells to Enhance the Therapeutic Efficacy of Adoptive T-Cell Therapy and Checkpoint Blockade.

Abstract
Adoptive cell therapy (ACT), based on treatment with autologous tumor infiltrating lymphocyte (TIL)-derived or genetically modified chimeric antigen receptor (CAR) T cells, has become a potentially curative therapy for subgroups of patients with melanoma and hematological malignancies. To further improve response rates, and to broaden the applicability of ACT to more types of solid malignancies, it is necessary to explore and define strategies that can be used as adjuvant treatments to ACT. Stimulation of endogenous dendritic cells (DCs) alongside ACT can be used to promote epitope spreading and thereby decrease the risk of tumor escape due to target antigen downregulation, which is a common cause of disease relapse in initially responsive ACT treated patients. Addition of checkpoint blockade to ACT and DC stimulation might further enhance response rates by counteracting an eventual inactivation of infused and endogenously primed tumor-reactive T cells. This review will outline and discuss therapeutic strategies that can be utilized to engage endogenous DCs alongside ACT and checkpoint blockade, to strengthen the anti-tumor immune response.
AuthorsMie Linder Hübbe, Ditte Elisabeth Jæhger, Thomas Lars Andresen, Mads Hald Andersen
JournalFrontiers in immunology (Front Immunol) Vol. 11 Pg. 578349 ( 2020) ISSN: 1664-3224 [Electronic] Switzerland
PMID33101304 (Publication Type: Journal Article, Review)
CopyrightCopyright © 2020 Hübbe, Jæhger, Andresen and Andersen.
Chemical References
  • Immune Checkpoint Inhibitors
Topics
  • Animals
  • Combined Modality Therapy
  • Dendritic Cells (drug effects, immunology, metabolism)
  • Humans
  • Immune Checkpoint Inhibitors (adverse effects, therapeutic use)
  • Immunotherapy, Adoptive
  • Neoplasms (drug therapy, immunology, metabolism)
  • T-Lymphocytes (immunology, metabolism, transplantation)
  • Treatment Outcome
  • Tumor Escape
  • Tumor Microenvironment

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