Induction of antigen-specific cytotoxic T lymphocytes by fusion cells generated from allogeneic plasmacytoid dendritic and tumor cells

Abstract

Previous work has demonstrated that fusion cells generated from autologous monocyte-derived dendritic cells (MoDCs) and whole tumor cells induce efficient antigen-specific cytotoxic T lymphocytes. A major limitation to the use of this strategy is the availability of adequate amounts of autologous tumor cells. Moreover, MoDCs from cancer patients are often defective in their antigen-processing and presentation machinery. In this study, two types of allogeneic cells, a leukemia plasmacytoid dendritic cell (pDC) line (PMDC05) and pancreatic cancer cell lines (PANC-1 or MIA PaCa-2), were fused instead of autologous MoDCs and tumor cells. We created four types of pDC/tumor fusion cells by alternating fusion partners and treating with lipopolysaccharide (LPS): i) PMDC05 fused with PANC-1 (pDC/PANC-1), ii) PMDC05 fused with MIA PaCa-2 (pDC/MIA PaCa-2), iii) LPS-stimulated pDC/PANC-1 (LPS-pDC/PANC-1) and iv) LPS-stimulated pDC/MIA PaCa-2 (LPS-pDC/MIA PaCa-2) and examined their antitumor immune responses. The LPS-pDC/tumor cell fusions were the most active, as demonstrated by their: i) upregulated expression of HLA-DR and CD86 on a per-fusion-cell basis, ii) increased production of IL-12p70, iii) generation of a higher percentage of IFN-γ-producing CD4⁺ and CD8⁺ T cells and iv) augmented induction of MUC1-specific CD8⁺ T cells that lyse target tumor cells. This study provides the first evidence for an in vitro induction of antigen-specific cytotoxic T lymphocytes by LPS-stimulated fusion cells generated from leukemia plasmacytoid DCs and tumor cells and suggests that this strategy has potential applicability to the field of adoptive immunotherapy.

Treatment of osteosarcoma with microwave thermal ablation to induce immunogenic cell death

“…Whole ablated tumor cells might serve as general cancer antigens, and hyperthermia-induced exposure to the composition of whole tumor cells might be a superior alternative to other well-known antigen-loading vaccines [28]. This study provided the foundations for an effective and broadly applicable treatment to a wide range of cancer indications for which tumor-associated antigens have not been identified.…”

Tumor Microenvironment and Cell Fusion

“…Researchers administer the fusion between dendritic cells and whole tumor cells by chemical, physical, or viral means and generate hybrids that display both known and unidentified TAAs originally expressed by whole tumor cells. Then, the dendritic-tumor hybrids process multiple TAAs endogenously and present antigenic peptides to both major histocompatibility complex classes I and II molecules to activate both CD4 + and CD8 + T cells, thus activating the antitumor immunity [81, 82, 102, 103]. Dendritic–tumor cell fusion provides strategies to produce dendritic-tumor cell fusion-based tumor vaccines to display immunotherapy for tumors.…”

Dendritic-Tumor Fusion Cell-Based Cancer Vaccines

“…DC-tumor FC vaccines with fully allogeneic components have been demonstrated to induce clinical responses [ 45 ]. Moreover, we have shown that fusion cells generated with an allogeneic DC line and allogeneic tumor cell line can induce antigen-specific CTL responses in vitro [ 46 ]. These findings introduce the possibility of using defined allogeneic DCs and allogeneic tumor lines to induce antigen-specific CTLs for adoptive immunotherapy.…”