Trial watch: Dendritic cell-based anticancer immunotherapy

ABSTRACT

Dendritic cell (DC)-based vaccines against cancer have been extensively developed over the past two decades. Typically DC-based cancer immunotherapy entails loading patient-derived DCs with an appropriate source of tumor-associated antigens (TAAs) and efficient DC stimulation through a so-called “maturation cocktail” (typically a combination of pro-inflammatory cytokines and Toll-like receptor agonists), followed by DC reintroduction into patients. DC vaccines have been documented to (re)activate tumor-specific T cells in both preclinical and clinical settings. There is considerable clinical interest in combining DC-based anticancer vaccines with T cell-targeting immunotherapies. This reflects the established capacity of DC-based vaccines to generate a pool of TAA-specific effector T cells and facilitate their infiltration into the tumor bed. In this Trial Watch, we survey the latest trends in the preclinical and clinical development of DC-based anticancer therapeutics. We also highlight how the emergence of immune checkpoint blockers and adoptive T-cell transfer-based approaches has modified the clinical niche for DC-based vaccines within the wide cancer immunotherapy landscape.

KEYWORDS:

• Antigen cross-presentation
• DAMPs
• immune-checkpoint blockers
• plasmacytoid dendritic cells
• TLR signaling
• tumor-infiltrating lymphocytes

Disclosure of potential conflicts of interest

LG provides remunerated consulting to OmniSEQ (Buffalo, NY).

Funding

ADG, MVP and MS are recipients of FWO Postdoctoral or Doctoral Fellowships from FWO-Vlaanderen, Belgium. PA is supported by grants from FWO (G060713N, G076617N), KU Leuven (C16/15/073) and Belgian State (IAP7/32). GK is supported by Ligue contre le Cancer (équipe labelisée); Agence National de la Recherche (ANR); Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; AXA Chair for Longevity Research; Institut National du Cancer (INCa); Fondation Bettencourt-Schueller; Fondation de France; Fondation pour la Recherche Médicale (FRM); the European Commission (ArtForce); the European Research Council (ERC); the LabEx Immuno-Oncology; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI). LG is supported by WCMC (intramural funds) and Sotio a.c. (Prague, Czech Republic)