Vectors encoding carcinoembryonic antigen fused to the B subunit of heat-labile enterotoxin elicit antigen-specific immune responses and antitumor effects

Facciabene, Andrea; Aurisicchio, Luigi; Elia, Leonardo; Palombo, Fabio; Mennuni, Carmela; Ciliberto, Gennaro; Monica, Nicola La

doi:10.1016/j.vaccine.2007.10.060

Cited by 34 publications

(38 citation statements)

References 37 publications

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“…To identify the best immunogen for vaccination, we tested three different forms of murine MMP11: wild type (MMP11 wt ), codon optimized (MMP11 opt ), and fused to the LTB (MMP11-LTB opt ). Codon optimization of cDNA has been shown to enhance expression and the induction of the immune response (27,34,35), whereas fusion to LTB increases antigen immunogenicity (24). To abrogate enzymatic activity, a point mutation was introduced in the latter two versions, changing glutamic acid to alanine at position 220 (11).…”

Section: Resultsmentioning

confidence: 99%

“…Vaccination against MMP11 exerts antitumor effects. In addition, the immunogenic potency of this antigen is enhanced by DNA electroporation and by the use of codon-optimized cDNA fused to immunomodulatory sequences of LTB (24). Therefore, it is not surprising that pV1J-MMP11-LTB opt is the most efficient among the different MMP11 derivatives in eliciting an immune response to the target antigen (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…pV1J-MMP11/LTBopt was constructed by PCR amplification of MMP11opt cDNA and cloning in plasmid pV1J-LTBopt, which contains the B subunit of Escherichia coli heat-labile enterotoxin (LTB) cDNA encompassing nucleotide 64 to 375 (amino acid 21 to 125; ref. 24).…”

Section: Methodsmentioning

confidence: 99%

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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: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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MMP11: A Novel Target Antigen for Cancer Immunotherapy

Peruzzi

Mori

Conforti

et al. 2009

Clinical Cancer Research

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“…All constructs were routinely sequenced by the DNA sequencing core facility at University of Pennsylvania, and Tem1 and TT constructs were confirmed with the correct sequences. DNA immunization was performed as described previously (79). Briefly, 50 μg plasmid in saline was injected i.m., and electrogene transfer was performed (2 pulses at 100 mV for 200 ms) immediately after injection.…”

Section: Discussionmentioning

confidence: 99%

“…To test whether Tem1-TT immunization affects mouse pregnancy by interfering with prenatal angiogenic processes, 6-to 8-week-old female mice were immunized 5 times as previously described (79). 1 week after the last immunization, mice were mated for 48 hours with individually housed males.…”

Section: Methodsmentioning

confidence: 99%