Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses

Avigan, David; Vasir, Baldev; Gong, Jianlin; Borges, Virginia F.; Wu, Zhiyou; Uhl, Lynne; Atkins, Michael B.; Mier, James W.; McDermott, David F.; Smith, Therese; Giallambardo, Nancy; Stone, Carolyn; Schadt, Kim; Dolgoff, Jennifer; Tetreault, Jean Claude; Villarroel, Marisa; Küfe, Donald

doi:10.1158/1078-0432.ccr-04-0347

Cited by 223 publications

(142 citation statements)

References 45 publications

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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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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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“…An early DC vaccine strategy for breast cancer involved the production of DC/tumor cell fusion vaccines. Avigen et al conducted a trial in which 16 patients with metastatic breast cancer were injected with a fusion vaccine using tumor cells obtained from a biopsy and DCs acquired from leukapheresis [88]. Three patients had a significant clinical response.…”

Section: Vaccination In Breast Cancermentioning

confidence: 99%

Targeting Molecular Pathways for Prevention of High Risk Breast Cancer: A Model for Cancer Prevention

Showalter¹,

Czerniecki²

2012

Cancer Prevention - From Mechanisms to Translational Benefits

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“…Obtained immature DCs can be pulsed with tumor cell lysates (Nair SK et al 1997) or synthetic peptides (Gitlitz et al, 2003), modified with genes encoding tumor antigens or tumor cells RNA (Ashley et al, 1997). For immunization are also used hybrids of DCs with tumor cells (Avigan et al, 2004). In a small trial, a group of 11 patients with advanced-stage melanoma were immunised with autologous DCs previously incubated with the MAGE-3 peptide presented by HLA-A1.…”

Section: Vaccines Based On Dendritic Cellsmentioning

confidence: 99%

Immunotargeting of Melanoma

Mackiewicz¹,

Maćkiewicz²

2011

Current Management of Malignant Melanoma

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Fusion Cell Vaccination of Patients with Metastatic Breast and Renal Cancer Induces Immunological and Clinical Responses

Abstract: Conclusions: Our findings demonstrate that fusion cell vaccination of patients with metastatic breast and renal cancer is a feasible, nontoxic approach associated with the induction of immunological and clinical antitumor responses.

Cited by 223 publications

References 45 publications

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

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

Targeting Molecular Pathways for Prevention of High Risk Breast Cancer: A Model for Cancer Prevention

Immunotargeting of Melanoma

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