Vaccination with Dendritic Cells Inhibits the Growth of Hepatic Metastases in B6 Mice

DeMatos, Pierre; Abdel-Wahab, Zeinab; Vervaert, Carol E.; Seigler, Hilliard F.

doi:10.1006/cimm.1998.1277

Cited by 37 publications

(18 citation statements)

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“…Often these studies have involved intratumor injection, although distantly injected unpulsed DC cause some tumoricidal activity in some models (17)(18)(19) and no activity in other studies (12)(13)(14)(15)(16), presumably reflecting differences in DC subtype and/or inherent antigenicity of the model. In our C57BL/6 model, bone marrow-derived unpulsed DC were generated by short-term culture from plastic-adherent monocytes, following addition of GM-CSF and IL-4 and activation with LPS (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In adoptive transfer studies stimulation of adaptive immunity has generally resulted from the priming of DC ex vivo with tumor Ags (7,8), although unprimed DC have shown effective tumoricidal activity in animal models following direct intratumoral injection (9 -11). In tumor models involving injection of DC at distant sites, unpulsed DC usually show low or no antitumor activity compared with Ag-pulsed DC (12)(13)(14)(15)(16). However, some studies have shown tumoricidal activity of unpulsed DC injected at sites distant to a tumor, attributed, at least in part, to stimulation of innate NK responses (4,(17)(18)(19).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

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Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Himoudi¹,

Nabarro²,

Buddle³

et al. 2008

The Journal of Immunology

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The CD11cintB220+NK1.1+CD49+ subset of cells has recently been described as IFN-producing killer dendritic cells (IKDC), which share phenotypic and functional properties of dendritic cells and NK cells. Herein we show that bone marrow-derived murine dendritic cell preparations contain abundant CD11cintB220+NK1.1+CD49+ cells, the removal of which results in loss of tumoricidal activity of unpulsed dendritic cells in vivo. Moreover, following s.c. injection, as few as 5 × 103 highly pure bone marrow-derived IKDC cells are capable of shrinking small contralateral syngeneic tumors in C57BL/6 mice, but not in immunodeficient mice, implying the obligate involvement of host effector cells in tumor rejection. Our data suggest that bone marrow-derived IKDC represent a population that has powerful tumoricidal activity in vivo.

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Section: Discussionmentioning

confidence: 99%

Section: Endritic Cells (Dc)mentioning

confidence: 99%

Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Himoudi¹,

Nabarro²,

Buddle³

et al. 2008

The Journal of Immunology

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“…1 Protective cellular immunity was induced by vaccination of DCs loaded with various forms of tumor antigens (Ag) in several animal models. [2][3][4] Early clinical trials using tumor Ag-pulsed DCs as vaccines for the treatment of various advanced malignancies have been reported. [5][6][7] Several DC-based clinical trials employed preidentified tumor-associated Ag (TAA) or synthetic peptides containing cytotoxic T lymphocyte (CTL) epitopes of known TAA as the source of Ag.…”

mentioning

confidence: 99%

Concurrent delivery of tumor antigens and activation signals to dendritic cells by irradiated CD40 ligand-transfected tumor cells resulted in efficient activation of specific CD8+ T cells

Liu

Cheng

et al. 2003

Cancer Gene Ther

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To improve the efficacy of tumor cell-based and dendritic cell (DC)-based cancer vaccines, this study explored the potential of a new cancer vaccine strategy, that is, the use of CD40 ligand-transfected tumor (CD40L-tumor) cells to simultaneously deliver both tumor-derived antigens (Ag) and maturation stimuli to DCs. Materials from frozen/thawed or irradiated human tumor cells, with or without surface CD40L, were internalized efficiently by immature DCs after coincubation. However, during the internalization process, only coculturing with irradiated CD40L-tumor cells resulted in concurrent, optimal DC maturation and production of proinflammatory chemokines and pro-Th1 cytokines, such as IL-6, IL-8, IL-12, IFN-g, and TNF-a. These activated DCs were the most potent cells to support the growth of CD8 þ , IFN-g-producing T cells, and to process tumor Ag for the generation of specific cytotoxic T cells in vitro. Animals vaccinated with irradiated CD40L-tumor cell-pulsed DCs were better protected against subsequent challenge of a weakly immunogenic tumor cell line than animals vaccinated with irradiated CD40L-tumor cells alone. Thus, our results strongly support the future clinical application of using DCs pulsed with irradiated CD40L-tumor cells as a cancer vaccine.

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“…The authors conclude that the DC-mediated NK cell activation was likely to be through an intermediate interaction of DCs with CD4 þ T cells rather than a direction effect on the NK cells. Furthermore, although small in number there have been other reports that unpulsed DCs can induce tumour protection (Yang et al, 1997;DeMatos et al, 1998). Interestingly, early studies by Knight (Knight et al, 1985) also suggested that normal syngeneic DCs could induce tumour regression or delayed tumour growth.…”

Section: Discussionmentioning

confidence: 99%

Immunisation with ‘naïve’ syngeneic dendritic cells protects mice from tumour challenge

et al. 2008

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Dendritic cells (DCs) 'pulsed' with an appropriate antigen may elicit an antitumour immune response in mouse models. However, while attempting to develop a DC immunotherapy protocol for the treatment of breast cancer based on the tumour-associated MUC1 glycoforms, we found that unpulsed DCs can affect tumour growth. Protection from RMA-MUC1 tumour challenge was achieved in C57Bl/6 MUC1 transgenic mice by immunising with syngeneic DCs pulsed with a MUC1 peptide. However, unpulsed DCs gave a similar level of protection, making it impossible to evaluate the effect of immunisation of mice with DCs pulsed with the specific peptide. Balb/C mice could also be protected from tumour challenge by immunisation with unpulsed DCs prior to challenge with murine mammary tumour cells (410.4) or these cells transfected with MUC1 (E3). Protection was achieved with as few as three injections of 50 000 naïve DCs per mouse per week, was not dependent on injection route, and was not specific to cell lines expressing human MUC1. However, the use of Rag2-knockout mice demonstrated that the adaptive immune response was required for tumour rejection. Injection of unpulsed DCs into mice bearing the E3 tumour slowed tumour growth. In vitro, production of IFN-g and IL-4 was increased in splenic cells isolated from mice immunised with DCs. Depleting CD4 T cells in vitro partially decreased cytokine production by splenocytes, but CD8 depletion had no effect. This paper shows that naïve syngeneic DCs may induce an antitumour immune response and has implications for DC immunotherapy preclinical and clinical trials.

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Vaccination with Dendritic Cells Inhibits the Growth of Hepatic Metastases in B6 Mice

Cited by 37 publications

References 50 publications

Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Bone Marrow-Derived IFN-Producing Killer Dendritic Cells Account for the Tumoricidal Activity of Unpulsed Dendritic Cells

Concurrent delivery of tumor antigens and activation signals to dendritic cells by irradiated CD40 ligand-transfected tumor cells resulted in efficient activation of specific CD8+ T cells

Immunisation with ‘naïve’ syngeneic dendritic cells protects mice from tumour challenge

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