In:
Journal for ImmunoTherapy of Cancer, BMJ, Vol. 9, No. Suppl 2 ( 2021-11), p. A232-A232
Abstract:
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. References 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. Leaf RK, et al . DCOne as an allogeneic cell-based vaccine for multiple myeloma. J Immunother 2017; 40 (9):315–322.
Type of Medium:
Online Resource
ISSN:
2051-1426
DOI:
10.1136/jitc-2021-SITC2021.219
Language:
English
Publisher:
BMJ
Publication Date:
2021
detail.hit.zdb_id:
2719863-7
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