Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2

Yi, Tao; Yq, Wei; Tian, Li; Zhao, Xia; Li, Jian; Deng, Hongxin; Yj, Wen; Ch, Zou; Tan, GH; Kan, Biao; Jm, Su; Jiang, Yu; Yq, Mao; Chen, P; Ys, Wang

doi:10.1038/sj.cgt.7700994

Cited by 18 publications

(14 citation statements)

References 27 publications

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“…The antitumoral effects of a vaccine against MMP2 have been reported (40). MMP-2 -specific autoantibodies were detected in sera of mice immunized with a tumor cell vaccine expressing chicken MMP2.…”

Section: Discussionmentioning

confidence: 93%

MMP11: A Novel Target Antigen for Cancer Immunotherapy

Peruzzi

Mori

Conforti

et al. 2009

Clinical Cancer Research

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Purpose: Matrix metalloproteinases (MMP) are zinc-dependent endopeptidases that mediate numerous physiologic and pathologic processes, including matrix degradation, tissue remodeling, inflammation, and tumor metastasis.To develop a vaccine targeting stromal antigens expressed by cancer-associated fibroblasts, we focused on MMP11 (or stromelysin 3). MMP11expression correlates with aggressive profile and invasiveness of different types of carcinoma. Experimental Design: To show the efficacy of a vaccine targeting MMP11, we constructed a series of plasmid DNA vectors expressing murine MMP11. Mice were vaccinated by i.m. injection followed by in vivo DNA electroporation. A chemically induced, MMP11-overexpressing colon cancer model was established and characterized. Antibody and T-cell responses were determined, and immunoreactive epitopes were characterized. To analyze the possible use of MMP11 as tumor-associated antigen in cancer patients, HLA-A2.1 transgenic mice (HHD) were used to identify reactive epitopes as tools to assess immunogenicity in humans.Results: Using microarray, we confirmed the overexpression of MMP11mRNA in a large panel of human tumor samples. MMP11vaccine induced cell mediated and antibody immune response and exerted significant antitumoral protection in mice with colon cancer in prophylactic and therapeutic settings. HHD transgenic mice were vaccinated with a plasmid encoding human MMP11, and a HLA-A2.1^restricted epitope (hMMP 237 ) was identified. hMMP 237 was shown to be immunogenic in human peripheral blood mononuclear cells (PBMC) by in vitro priming. Conclusion: Our study describes the identification of MMP11as a novel broadly expressed tumor associated antigen as target candidate for cancer immunotherapy.

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Section: Discussionmentioning

confidence: 93%

MMP11: A Novel Target Antigen for Cancer Immunotherapy

Peruzzi

Mori

Conforti

et al. 2009

Clinical Cancer Research

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“…Immunologic targeting of MMPs has been suggested in several studies. The antitumoral effects of a vaccine against MMP2 have been reported [8]. MMP7 was identified as a novel broadly expressed tumor-associated antigen and a T-cell epitope derived from this protein was proposed as candidate for vaccine development [9].…”

Section: Introductionmentioning

confidence: 99%

Circulating MMP11 and specific antibody immune response in breast and prostate cancer patients

Roscilli¹,

Cappelletti²,

Vitis

et al. 2014

J Transl Med

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BackgroundTumor Associated Antigens are characterized by spontaneous immune response in cancer patients as a consequence of overexpression and epitope-presentation on MHC class I/II machinery. Matrix Metalloprotease 11 (MMP11) expression has been associated with poor prognosis for several cancer types, including breast and prostate cancer.MethodsMMP11 expression was determined by immunoistochemistry in breast and prostate cancer samples. Circulating MMP11 protein as well as the spontaneous immune responses against MMP11 were analyzed in a set of breast and prostate cancer patients.ResultsIn plasma samples MMP11 protein was present in 5/13 breast cancer patients and in 1/12 prostate cancer patients. An antibody response was observed in 7/13 breast cancer patients and in 3/12 prostate cancer patients.ConclusionsThese findings further suggest MMP11 as a promising biomarker for these tumor types and a suitable target for cancer immunotherapy strategies.

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“…The possible mFlk-1 -specific cytotoxicity mediated by CTLs was determined by 51 Cr release assay as described previously (12,32). Briefly, C57BL/6J mice were immunized with 100-Ag DNA as described above.…”

Section: Methodsmentioning

confidence: 99%

Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine β-Defensin 2 and mFlk-1

Wang¹,

Wang²,

Wang³

et al. 2007

Clinical Cancer Research

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Purpose: Previous studies indicated that humoral or cellular immunity against murine vascular endothelial growth factor 2 (mFlk-1) was elicited to inhibit tumor growth. Here we describe a genetic fusion vaccine, pMBD2-mFlk-1, based on the targeting of a modified mFlk-1 to antigenpresenting cells by a murine h-defensin 2 (MBD2) protein to induce both humoral and cellular immunity against mFlk-1, with the targeting especially focused on immature dendritic cells. Experimental Design:The protective and therapeutic antitumor immunity of the fusion vaccine was investigated in mouse models. Antiangiogenesis effect was detected by immunohistochemical staining and alginate-encapsulate tumor cell assay. The mechanisms of the fusion vaccine were primarily explored by detection of autoantibodies and CTL activity and confirmed by the deletion of immune cell subsets. Results: The fusion vaccine elicited a strong protective and therapeutic antitumor immunity through antiangiogenesis in mouse models, and this worked through stimulation of an antigenspecific CD8 + T-cell response as well as a specific B-cell response against mFlk-1. The findings were confirmed by depletion of immune cell subsets and in knockout mice. Conclusion: Our study showed that a fusion vaccine based on self immune peptide (MBD2) and self antigen (mFlk-1) induced autoimmunity against endothelial cells, resulting in inhibition of tumor growth, and could be further exploited in clinical applications of cancer immunotherapy.

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Humoral and cellular immunity induced by tumor cell vaccine based on the chicken xenogeneic homologous matrix metalloproteinase-2

Cited by 18 publications

References 27 publications

MMP11: A Novel Target Antigen for Cancer Immunotherapy

MMP11: A Novel Target Antigen for Cancer Immunotherapy

Circulating MMP11 and specific antibody immune response in breast and prostate cancer patients

Immunity against Tumor Angiogenesis Induced by a Fusion Vaccine with Murine β-Defensin 2 and mFlk-1

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