Induction of Antitumor Immunity by Semi‐Allogeneic and Fully Allogeneic Electrofusion Products of Tumor Cells and Dendritic Cells

Siders, William; Garron, Carrie; Shields, Jacqueline D.; Kaplan, Johanne

doi:10.1111/j.1752-8062.2008.00052.x

Cited by 8 publications

(5 citation statements)

References 23 publications

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Section: Discussionmentioning

confidence: 99%

“…Adoptive immunotherapy using tumor-reactive T lymphocytes has emerged as a powerful approach for the treatment of bulky, refractory cancer [ 34 , 35 ]. DC-based vaccination to activate T cells, which is one main form of adoptive immunotherapy, has been shown to effectively mediate antitumor immunity [ 36 ]. DC-based immunotherapy can be approached in one of two ways: direct immunization with antigen (tumor-associated proteins, peptides, or tumor lysates) pulsed DCs or adoptive transfer of in vitro expanded CTLs following stimulations with antigen-pulsed DCs.…”

Section: Discussionmentioning

confidence: 99%

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Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

et al. 2014

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The epidermal growth factor receptor (EGFR) mutant of EGFRvIII is highly expressed in glioma cells, and the EGFRvIII-specific dendritic cell (DC)-induced tumor antigen-specific CD8+ cytotoxic T lymphocytes (CTLs) may hold promise in cancer immunotherapy. Interferon (IFN)-γ-inducible protein (IP)-10 (IP-10) is a potent inhibitor of angiogenesis and can recruit CXCR3+ T cells, including CD8+ T cells, which are important for the control of tumor growth. In this study, we assessed if the combination of IP10-EGFRvIIIscFv with DC-induced CTLs would improve the therapeutic antitumor efficacy. IP10-scFv was generated by linking the human IP-10 gene with the DNA fragment for anti-EGFRvIIIscFv with a (Gly4Ser)3 flexible linker, purified by affinity chromatography, and characterized for its anti-EGFRvIII immunoreactivity and chemotactic activity. DCs were isolated from human peripheral blood monocyte cells and pulsed with EGFRvIII-peptide, then co-cultured with autologous CD8+ T cells. BALB/c-nu mice were inoculated with human glioma U87-EGFRvIII cells in the brain and treated intracranially with IP10-scFv and/or intravenously with DC-induced CTLs for evaluating the therapeutic effect. Treatment with both IP10-scFv and EGFRvIII peptide-pulsed, DC-induced CTL synergistically inhibited the growth of glioma and prolonged the survival of tumor-bearing mice, which was accompanied by the inhibition of tumor angiogenesis and enhancement of cytotoxicity, thereby increasing the numbers of brain-infiltrating lymphocytes (BILs) and prolonging the residence time of CTLs in the tumor.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

et al. 2014

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“…These findings introduce the possibility of using defined allogeneic DCs and allogeneic tumor lines to induce antigen-specific CTLs for adoptive immunotherapy. Although DC-tumor FCs generated with fully syngeneic components may be most effective for antigen-specific CTL induction, semi-allogeneic and fully-allogeneic components may also have potential in the field of adoptive immunotherapy [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

Dendritic-Tumor Fusion Cell-Based Cancer Vaccines

Koido

2016

IJMS

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Dendritic cells (DCs) are potent antigen-presenting cells (APCs) that play a critical role in the induction of antitumor immunity. Therefore, various strategies have been developed to deliver tumor-associated antigens (TAAs) to DCs as cancer vaccines. The fusion of DCs and whole tumor cells to generate DC-tumor fusion cells (DC-tumor FCs) is an alternative strategy to treat cancer patients. The cell fusion method allows DCs to be exposed to the broad array of TAAs originally expressed by whole tumor cells. DCs then process TAAs endogenously and present them through major histocompatibility complex (MHC) class I and II pathways in the context of costimulatory molecules, resulting in simultaneous activation of both CD4+ and CD8+ T cells. DC-tumor FCs require optimized enhanced immunogenicity of both DCs and whole tumor cells. In this context, an effective fusion strategy also needs to produce immunogenic DC-tumor FCs. We discuss the potential ability of DC-tumor FCs and the recent progress in improving clinical outcomes by DC-tumor FC-based cancer vaccines.

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“…Moreover, allogeneic tumor cell lines have been used in fusion cell vaccines in both preclinical (25,29,30) and clinical studies (31) and a MoDC/tumor fusion cell vaccine with fully allogeneic components has been demonstrated to induce clinical responses (31). Therefore, DC/tumor fusions generated with fully syngeneic, semi-allogeneic or fully allogeneic components are effective in inducing antigen-specific, long-lasting antitumor immunity (32).…”

Section: Discussionmentioning

confidence: 99%

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

Koido

Homma

Kan

et al. 2014

International Journal of Oncology

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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.

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Induction of Antitumor Immunity by Semi‐Allogeneic and Fully Allogeneic Electrofusion Products of Tumor Cells and Dendritic Cells

Cited by 8 publications

References 23 publications

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

Human IP10-scFv and DC-induced CTL synergistically inhibit the growth of glioma in a xenograft model

Dendritic-Tumor Fusion Cell-Based Cancer Vaccines

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

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