219 CD47 and phosphatidylserine contribute to the interaction between antigen presenting cells and the allogeneic cell-based relapse vaccine DCP-001

Background DCP-001 is a cancer relapse vaccine derived from the DCOne® human leukemic cell line. During manufacturing, cells are shifted towards mature dendritic (mDC) phenotype, combining an endogenous tumor antigen repertoire (e.g. WT-1, RHAMM and PRAME) with mDC costimulatory profile providing basis for highly immunogenic DCP-001. In phase I clinical study in acute myeloid leukemia (AML), demonstrated to be safe induce multifunctional antitumor immune responses. 1 It has also been reported that induces immunity against multiple myeloma peripheral blood mononuclear (PBMC) patients antigenic material transferred host presenting (APC), possibly via extracellular vesicles. 2 However, possibility of direct interactions between APC not yet investigated. Methods To further elucidate mode action DCP-001, we studied PBMC isolated immature monocyte-derived DCs (iMoDC) vitro co-culture studies. A skin explant model was used determine uptake by migrating after intradermal injection. Results We found stimulates secretion various proinflammatory cytokines (IL-1β, GM-CSF, IFN-γ, IL-2, TNF-α, IL-6) chemokines (IL-8 RANTES) PBMC. addition, demonstrate efficiently taken up iMoDC cell-cell this phagocytic process influenced ”eat-me” ”don’t eat me” signaling pathways. Blocking signals calreticulin phosphatidylserine inhibited whereas blockade signal CD47 enhanced uptake. After injection ex-vivo model, its skin-emigrating as well simultaneous activation these DCs. Conclusions Our data suggest key role triggering responses upon vaccination. provide rationale potential combination therapies based on inhibitors pathway. References van de Loosdrecht AA, et al . novel allogeneic off-the-shelf post-remission treatment elderly leukemia. Cancer Immunol Immunother 2018; 67 (10):1505–1518. Leaf RK, DCOne cell-based myeloma. J 2017; 40 (9):315–322.