Abstract
DCP-001 is a cell-based cancer vaccine generated by differentiation and maturation of cells from the human DCOne myeloid leukemic cell line. This results in a vaccine comprising a broad array of endogenous tumor antigens combined with a mature dendritic cell (mDC) costimulatory profile, functioning as a local inflammatory adjuvant when injected into an allogeneic recipient. Intradermal DCP-001 vaccination has been shown to be safe and feasible as a post-remission therapy in acute myeloid leukemia. In the current study, the mode of action of DCP-001 was further characterized by static and dynamic analysis of the interaction between labelled DCP-001 and host antigen-presenting cells (APCs). Direct cell–cell interactions and uptake of DCP-001 cellular content by APCs were shown to depend on DCP-001 cell surface expression of calreticulin and phosphatidylserine, while blockade of CD47 enhanced the process. Injection of DCP-001 in an ex vivo human skin model led to its uptake by activated skin-emigrating DCs. These data suggest that, following intradermal DCP-001 vaccination, local and recruited host APCs capture tumor-associated antigens from the vaccine, become activated and migrate to the draining lymph nodes to subsequently (re)activate tumor-reactive T-cells. The improved uptake of DCP-001 by blocking CD47 rationalizes the possible combination of DCP-001 vaccination with CD47 blocking therapies.
Original language | English |
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Article number | 3233 |
Journal | Cells |
Volume | 10 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2021 |
Keywords
- Acute myeloid leukemia
- Allogeneic
- Allogeneic Cells/immunology
- Antigen transfer
- Antigen-Presenting Cells/immunology
- CD47
- CD47 Antigen/antagonists & inhibitors
- Cancer Vaccines/immunology
- Cell Differentiation
- Cell Membrane/metabolism
- Cell-based vaccine
- Chemokines/metabolism
- DCOne
- DCP-001
- Dendritic Cells/immunology
- Dendritic cell
- Humans
- Inflammation/pathology
- Intradermal
- Models, Biological
- Phagocytosis
- Phenotype
- Phosphatidylserine
- Phosphatidylserines/metabolism
- Pinocytosis
- Signal Transduction