Article Text

Download PDFPDF

219 CD47 and phosphatidylserine contribute to the interaction between antigen presenting cells and the allogeneic cell-based relapse vaccine DCP-001
  1. Haoxiao Zuo1,
  2. Satwinder Kaur Singh1,
  3. Marie-José Van Lierop1,
  4. Jorn Kaspers1,
  5. Remco Bos1,
  6. Alwin Kamermans2,
  7. Helga E de Vries2,
  8. Tanja de Gruijl2,
  9. Ada Kruisbeek1,
  10. Erik Manting1 and
  11. Satwinder Kaur Singh1
  1. 1Immunicum AB, Leiden, Netherlands
  2. 2Amsterdam University Medical Center, Amsterdam, Netherlands


Background DCP-001 is a cancer relapse vaccine derived from the DCOne® human leukemic cell line. During manufacturing, DCOne® cells are shifted towards a mature dendritic cell (mDC) phenotype, combining an endogenous tumor antigen repertoire (e.g. WT-1, RHAMM and PRAME) with a mDC costimulatory profile and providing the basis for the highly immunogenic vaccine DCP-001. In a phase I clinical study in acute myeloid leukemia (AML), DCP-001 demonstrated to be safe and to induce multifunctional antitumor immune responses.1 It has also been reported that DCP-001 induces antitumor immunity against multiple myeloma cells in peripheral blood mononuclear cells (PBMC) from multiple myeloma patients and that DCP-001 antigenic material is transferred to host antigen presenting cells (APC), possibly via extracellular vesicles.2 However, the possibility of direct interactions between DCP-001 and host APC has not yet been investigated.

Methods To further elucidate the mode of action of DCP-001, we studied the interactions of DCP-001 with human PBMC and isolated immature monocyte-derived DCs (iMoDC) in in vitro co-culture studies. A human skin explant model was used to determine uptake of DCP-001 by migrating skin DCs after intradermal injection.

Results We found that DCP-001 stimulates the secretion of various proinflammatory cytokines (IL-1β, GM-CSF, IFN-γ, IL-2, TNF-α, and IL-6) and chemokines (IL-8 and RANTES) in PBMC. In addition, we demonstrate that DCP-001 is efficiently taken up by iMoDC via direct cell-cell interactions and that this phagocytic process is influenced by ”eat-me” and ”don’t eat me” signaling pathways. Blocking of the ”eat-me” signals calreticulin and phosphatidylserine inhibited the uptake of DCP-001, whereas blockade of the ”don’t eat me” signal CD47 enhanced DCP-001 uptake. After intradermal injection of DCP-001 in an ex-vivo human skin model, its uptake by skin-emigrating DCs was demonstrated as well as simultaneous activation of these DCs.

Conclusions Our data suggest a key role for host antigen presenting cells in the triggering of immune responses upon DCP-001 vaccination. In addition, the data provide rationale for potential combination therapies based on DCP-001 and inhibitors of the CD47 pathway.


  1. van de Loosdrecht AA, et al. A novel allogeneic off-the-shelf dendritic cell vaccine for post-remission treatment of elderly patients with acute myeloid leukemia. Cancer Immunol Immunother 2018;67(10):1505–1518.

  2. Leaf RK, et al. DCOne as an allogeneic cell-based vaccine for multiple myeloma. J Immunother 2017;40(9):315–322.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.