p53 autoantibodies from patients with head and neck cancer recognise common epitopes on the polypeptide chain of p53

Saleh, Jumana; Brunner, Christian; Gölzer, Ramona; Nastainczyk, Wolfgang; Montenarh, Mathias

doi:10.1016/j.canlet.2005.02.040

Cited by 12 publications

(56 citation statements)

References 18 publications

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“…ϩ T cells using wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide-pulsed DC as APC wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide-specific CD4 ϩ T cell lines were generated using autologous DC that had been matured in the presence of IL-1␤, IL-6, and TNF-␣ (10 ng/ml each) (PeproTech) for 24 h, harvested, resuspended (1 ϫ 10 6 cells/ml) in AIM-V medium containing 20 g/ml peptide, and incubated at 37°C for 4 h. Subsequently, the peptide-pulsed DC were irradiated (3000 rad), washed, and resuspended in AIM-V medium containing 5% (v/v) human AB serum. Autologous naive CD4 ϩ T cells were isolated by positive selection from nonadherent PBMC using CD4 MicroBeads and served as responder cells.…”

Section: Ivs Of Cd4mentioning

confidence: 99%

“…First, wt p53 [25][26][27][28][29][30][31][32][33][34][35] -specific helper cells were generated as follows: matured DC, obtained from PBMC of HLA-A2 ϩ /DR4 Ϫ normal donors, were resuspended at the concentration 1 ϫ 10 6 cells/ml in AIM-V medium containing 40 g/ml wt p53 264 -272 peptide and 20 g/ml wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide, and incubated at 37°C for 4 h. The peptide-pulsed DC and autologous peptide-specific CD4 ϩ T cells were irradiated (3000 rad), washed, and resuspended in AIM-V medium containing 5% (v/v) human AB serum. Next, autologous CD8-enriched PBMCs were negatively isolated from nonadherent PBMC using CD4 MicroBeads.…”

Section: Generation Of Wt P53 264 -272 -Specific Cd8mentioning

confidence: 99%

“…A panel of 14 wt p53 peptides, 13 of which were predicted by the TERITOPE algorithm (12) to bind to multiple HLA-DR allelic molecules, were tested (Table I). The wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide was tested also because it overlapped the algorithm-predicted wt p53 [22][23][24][25][26][27][28][29][30][31][32][33][34] peptide and may be a HLA-A2-restricted, CTL-defined wt p53 peptide (20). It was, therefore, possible that it might be a helper as well as cytotoxic peptide.…”

Section: In Two Sets Of Experiments Ivs Of Cd4mentioning

confidence: 99%

“…Following IVS with autologous DC transfected with either wt or mutant p53 cDNA, the outgrowing lymphocytes were tested for reactivity against a panel of peptides, which were algorithm-predicted to bind to multiple HLA-DR allelic molecules (12). These experiments resulted in the identification of the wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide as a naturally presented, Th cell-defined peptide that can induce/expand CD4 ϩ Th cells that are restricted, at minimum, by HLA-DR7, -11 alleles. The average frequencies of expression of these alleles are 14 and 15.5%, respectively, and comparable to that of the HLA-DR4 allele, which is 24.4% (11).…”

mentioning

confidence: 99%

“…The average frequencies of expression of these alleles are 14 and 15.5%, respectively, and comparable to that of the HLA-DR4 allele, which is 24.4% (11). Consequently, the identification of the wt p53 [25][26][27][28][29][30][31][32][33][34][35] and p53 110 -124 peptides increases the percentage of HLA-A2 ϩ subjects eligible to receive a multiepitope p53 peptide-based vaccine incorporating a p53 helper peptide to Ͼ50%. Furthermore, the ability of anti-wt p53 [25][26][27][28][29][30][31][32][33][34][35] Th cells to enhance ex vivo the generation of HLA-A2-restricted, anti-wt p53 264 -272 CD8 ϩ T cells is demonstrated, thereby providing the proof-of-principle that the helper activity of the wt p53 [25][26][27][28][29][30][31][32][33][34][35] peptide is likely to benefit p53-targeted immune responses and thus should be considered as a component of p53-based immunotherapy in the future.…”

mentioning

confidence: 99%

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The Wild-Type Sequence (wt) p5325–35 Peptide Induces HLA-DR7 and HLA-DR11-Restricted CD4+ Th Cells Capable of Enhancing the Ex Vivo Expansion and Function of Anti-wt p53264–272 Peptide CD8+ T Cells

Ito

Albers

Zhao

et al. 2006

The Journal of Immunology

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Tumor peptide-based vaccines are more effective when they include tumor-specific Th cell-defined as well as CTL-defined peptides. Presently, two overlapping wild-type sequences (wt) p53 helper peptides, p53108–122 and p53110–124, have been identified as HLA-DR1- and/or HLA-DR4-restricted epitopes. These HLA-DR alleles are expressed by ∼35% of subjects with cancer. To identify Th cell-defined wt p53 peptides suitable for use on the remaining subject population, a dendritic cell (DC)-based coculture system was developed. CD4+ T cells isolated from PBMC obtained from HLA-DR4− normal donors were stimulated ex vivo with autologous DC transfected with wt p53 or mutant p53 cDNA. Reactivity of T cells was tested in ELISPOT IFN-γ assays against DC pulsed individually with a panel of algorithm-predicted, multiple HLA-DR-binding wt p53 peptides. The wt p5325–35 peptide was identified as capable of inducing and being recognized by CD4+ T cells in association, at a minimum, with HLA-DR7 and -DR11 molecules, each of which is expressed by ∼15% of the population. In addition, the presence of anti-p5325–35 CD4+ Th cells was shown to enhance the in vitro generation/expansion of HLA-A2-restricted, anti-wt p53264–272 CD8+ T cells, which from one donor were initially “nonresponsive” to the wt p53264–272 peptide. The wt p5325–35 peptide has attributes of a naturally presented Th cell-defined peptide, which could be incorporated into antitumor vaccines applicable to a broader population of subjects for whom a wt p53 helper peptide is presently unavailable, as well as used for monitoring anti-p53 Th cell activity in cancer subjects receiving p53-based immunotherapy.

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Section: Ivs Of Cd4mentioning

confidence: 99%

Section: Generation Of Wt P53 264 -272 -Specific Cd8mentioning

confidence: 99%

Section: In Two Sets Of Experiments Ivs Of Cd4mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

The Wild-Type Sequence (wt) p5325–35 Peptide Induces HLA-DR7 and HLA-DR11-Restricted CD4+ Th Cells Capable of Enhancing the Ex Vivo Expansion and Function of Anti-wt p53264–272 Peptide CD8+ T Cells

Ito

Albers

Zhao

et al. 2006

The Journal of Immunology

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Multiplexed VeraCode bead-based serological immunoassay for colorectal cancer

Ostendorff

Awad

Braunschweiger

et al. 2013

Journal of Immunological Methods

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Colorectal cancer (CRC) is the second leading cause of cancer deaths in the U.S and Western world. Despite increased screening and advances in treatment, the mortality rate (ca. 50,000/year) and high national health-care burden for CRC are likely to remain high unless an effective non-invasive screening test for CRC is instituted for a large segment of the population. Blood-based protein biomarkers hold great promise for early disease diagnosis and personalized medicine; yet robust and reproducible multiplexing platforms and methodologies have lagged behind their genomic counterparts. Here, we report the development of a novel, multiplexed, hybrid immunoassay for CRC that is formatted on barcoded VeraCode™ micro-beads, which have until now only been used for genomic assays. The method combines a sandwich immunoassay format for detection of serum protein biomarkers with an antigen assay for autoantibody detection. The serum protein biomarkers CEA and GDF15 as well as autoantibodies to the p53 tumor associated antigen (TAA) were used to exemplify the method. This multiplex biomarker panel was configured to run on Illumina’s holographically barcoded VeraCode™ micro-bead platform, which is capable of measuring hundreds of analytes simultaneously in a single well from small volumes of blood (<50 μL) using a 96-well industry standard microtiter plate. This novel use of the VeraCode™ micro-bead platform translates into a potentially low volume, high throughput, multiplexed assay for CRC, for the purposes of biomarker validation, as well as patient screening, diagnostics and prognostics. In an evaluation of a 186 patient sera training set (CRC and normal), we obtained a diagnostic sensitivity of 54% and a specificity of 98%. We anticipate that by expanding and refining the biomarkers in this initial panel, and performing more extensive clinical validations, such an assay could ultimately provide a basis for CRC population screening to complement the more invasive, expensive and low throughput (but highly sensitive and specific) colonoscopy.

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The usefulness of new serum tumor markers in head and neck squamous cell carcinoma

Marcos

Martı́nez

Toyos

et al. 2009

Otolaryngol.--head neck surg.

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p53 autoantibodies from patients with head and neck cancer recognise common epitopes on the polypeptide chain of p53

Cited by 12 publications

References 18 publications

The Wild-Type Sequence (wt) p5325–35 Peptide Induces HLA-DR7 and HLA-DR11-Restricted CD4+ Th Cells Capable of Enhancing the Ex Vivo Expansion and Function of Anti-wt p53264–272 Peptide CD8+ T Cells

The Wild-Type Sequence (wt) p5325–35 Peptide Induces HLA-DR7 and HLA-DR11-Restricted CD4+ Th Cells Capable of Enhancing the Ex Vivo Expansion and Function of Anti-wt p53264–272 Peptide CD8+ T Cells

Multiplexed VeraCode bead-based serological immunoassay for colorectal cancer

The usefulness of new serum tumor markers in head and neck squamous cell carcinoma

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