Cancer immunotherapy by fusions of dendritic and tumour cells and rh‐IL‐12

Homma, Sadamu; Kikuchi, Tetsuro; Ishiji, N.; Ochiai, Kazuhiko; Takeyama, Hiroshi; Saotome, Hideo; Sagawa, Yukiko; Hara, Eiichi; Küfe, Donald; Ryan, John L.; Ohno, Tsuneya; Toda, Gotaro

doi:10.1111/j.1365-2362.2005.01494.x

Cited by 35 publications

(30 citation statements)

References 34 publications

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“…However, immune response or immune memory against tumor antigens might have later arisen systemically because the disappearance or shrinkage in size of tumors was found at areas distant from the treated tumor, and no metastasis in any other organs was found. Other cytokines which have been used together with DCs in clinical treatment are IL-2 and IL-12 (32)(33)(34)(35). Like IFNγ, these cytokines also polarize immune responses to T helper type 1, but their effect on clinical response and immune responses against tumors was less clear than that of IFNγ found in the present study.…”

Section: Discussioncontrasting

confidence: 55%

IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models

et al. 2010

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Dendritic cell (DC)-based immunotherapy can trigger effective immune responses against cancer in human patients. Although accompanied by little toxicity, further improvements are needed to optimize immune responses for fully satisfactory clinical outcomes. IFNγ, a potent inducer of T helper type 1 immune responses, is considered an important tool to realize improvements. In this study, we sought to clarify the effect of IFNγ on the maturation and activation of DCs and the clinical outcome of DC-based cancer therapy in dogs.

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Section: Discussioncontrasting

confidence: 55%

IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models

et al. 2010

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“…We have reported that fusions of monocyte-derived immature DCs and autologous breast cancer, ovarian cancer, acute myeloid leukemia, or colorectal cancer cells induce antitumor immune responses against autologous tumor in vitro (10,(12)(13)(14)(15)(16). In phase I clinical trials in patients with melanoma, glioma, gastric, breast, and renal cancer, vaccination with DCs/tumor FCs was associated with immunologic and clinical responses (17)(18)(19)(20)(21)(22). Although the DCs/tumor fusion strategy has enormous potential in mice study, results from early clinical trails have been unsatisfactory (8 -11, 17-22).…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Streptococcal Preparation OK-432 Promotes Fusion Efficiency and Enhances Induction of Antigen-Specific CTL by Fusions of Dendritic Cells and Colorectal Cancer Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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Dendritic/tumor fusion cell (FC) vaccine is an effective approach for various types of cancer but has not yet been standardized. Antitumor activity can be modulated by different mechanisms such as dendritic cell (DC) maturation state. This study addressed optimal strategies for FC preparations to enhance Ag-specific CTL activity. We have created three types of FC preparations by alternating fusion cell partners: 1) immature DCs fused with autologous colorectal carcinoma cells (Imm-FCs); 2) Imm-FCs followed by stimulation with penicillin-inactivated Streptococcus pyogenes (OK-432) (Imm-FCs/OK); and 3) OK-432-stimulated DCs directly fused to autologous colorectal carcinoma cells (OK-FCs). Both OK-FCs and Imm-FCs/OK coexpressed the CEA, MUC1, and significantly higher levels of CD86, CD83, and IL-12 than those obtained with Imm-FCs. Short-term culture of fusion cell preparations promoted the fusion efficiency. Interestingly, OK-FCs were more efficient in stimulating CD4+ and CD8+ T cells capable of high levels of IFN-γ production and cytolysis of autologous tumor or semiallogeneic targets. Moreover, OK-FCs are more effective inducer of CTL activation compared with Imm-FCs/OK on a per fusion cell basis. The pentameric assay confirmed that CEA- and MUC1-specific CTL was induced simultaneously by OK-FCs at high frequency. Furthermore, the cryopreserved OK-FCs retained stimulatory capacity for inducing antitumor immunity. These results suggest that OK-432 promotes fusion efficiency and induction of Ag-specific CTL by fusion cells. We conclude that DCs fused after stimulation by OK-432 may have the potential applicability to the field of antitumor immunotherapy and may provide a platform for adoptive immunotherapy in the clinical setting.

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“…We have previously reported that immature (Imm) DCs (Imm-DCs) fused with autologous tumor cells can induce Ag-specific polyclonal CTLs in vitro (7)(8)(9)(10)(11). Although immunization with DC/tumor cell FCs in patients with cancer has been associated with immunological responses in phase I clinical trials, early clinical trials have shown only limited success (12)(13)(14)(15)(16)(17). Because this DC/tumor cell FC approach was developed in animal studies, many adjuvants, including IL-2, IL-12, IL-18, and synthetic oligodeoxynucleotides (ODNs) containing specific bacterial unmethylated CpG motifs (CpG ODNs), have been used to enhance the ability of DC/tumor cell FC vaccines to evoke antitumor immune responses (18 -22).…”

Section: Synergistic Induction Of Antigen-specific Ctl By Fusions Of mentioning

confidence: 99%

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

Koido

Hara

Homma

et al. 2007

The Journal of Immunology

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Dendritic cell (DC)/tumor cell fusion cells (FCs) can induce potent CTL responses. The therapeutic efficacy of a vaccine requires the improved immunogenicity of both DCs and tumor cells. The DCs stimulated with the TLR agonist penicillin-killed Streptococcus pyogenes (OK-432; OK-DCs) showed higher expression levels of MHC class I and II, CD80, CD86, CD83, IL-12, and heat shock proteins (HSPs) than did immature DCs. Moreover, heat-treated autologous tumor cells displayed a characteristic phenotype with increased expression of HSPs, carcinoembryonic Ag (CEA), MUC1, and MHC class I (HLA-A2 and/or A24). In this study, we have created four types of FC preparation by alternating fusion cell partners: 1) immature DCs fused with unheated tumor cells; 2) immature DCs fused with heat-treated tumor cells; 3) OK-DCs fused with unheated tumor cells; and 4) OK-DCs fused with heat-treated tumor cells. Although OK-DCs fused with unheated tumor cells efficiently enhanced CTL induction, OK-DCs fused with heat-treated tumor cells were most active, as demonstrated by: 1) up-regulation of multiple HSPs, MHC class I and II, CEA, CD80, CD86, CD83, and IL-12; 2) activation of CD4+ and CD8+ T cells able to produce IFN- γ at higher levels; 3) efficient induction of CTL activity specific for CEA or MUC1 or both against autologous tumor; and 4) superior abilities to induce CD107+IFN-γ+CD8+ T cells and CD154+ IFN-γ+CD4+ T cells. These results strongly suggest that synergism between OK-DCs and heat-treated tumor cells enhances the immunogenicity of FCs and provides a promising means of inducing therapeutic antitumor immunity.

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Cancer immunotherapy by fusions of dendritic and tumour cells and rh‐IL‐12

Abstract: Immunotherapy using a FC vaccine and rhIL-12 induced no serious adverse reactions, and provided good therapeutic responses in some of the patients with a brain tumour.

Cited by 35 publications

References 34 publications

IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models

IFNγ Markedly Cooperates with Intratumoral Dendritic Cell Vaccine in Dog Tumor Models

Streptococcal Preparation OK-432 Promotes Fusion Efficiency and Enhances Induction of Antigen-Specific CTL by Fusions of Dendritic Cells and Colorectal Cancer Cells

Synergistic Induction of Antigen-Specific CTL by Fusions of TLR-Stimulated Dendritic Cells and Heat-Stressed Tumor Cells

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