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  • 1
    Keywords: PEPTIDE ; CELLS ; BLOOD ; CELL ; CLINICAL-TRIAL ; COMBINATION ; Germany ; PHASE-I ; DISEASE ; NEW-YORK ; PROTEIN ; SAMPLE ; SAMPLES ; PATIENT ; RESPONSES ; IMPACT ; primary ; INDUCTION ; ANTIGEN ; DENDRITIC CELLS ; T cell ; T cells ; T-CELL ; T-CELLS ; MHC ; TRIAL ; ASSAY ; tumor-infiltrating lymphocytes ; MELANOMA ; METASTATIC MELANOMA ; VACCINES ; HIGH-RISK ; PEPTIDES ; CLASS-I ; MHC class I ; VACCINE ; ELISPOT ; ELISPOT-ASSAY ; IMMUNE-RESPONSE ; vaccination ; MELANOMA PATIENTS ; IMMUNOGENICITY ; PERIPHERAL-BLOOD ; ADJUVANT ; CTL ; COLONY-STIMULATING FACTOR ; GM-CSF ; GRANULOCYTE-MACROPHAGE ; phase I studies ; GAMMA-ELISPOT ASSAY ; T-cell response ; tumor vaccine
    Abstract: Immunologic adjuvants are used to augment the immunogenicity of MHC class I-restricted peptide vaccines, but this effect has rarely been systematically evaluated in a clinical trial. We have investigated, in a phase I study, whether addition of the 2 adjuvants GM-CSF and KLH can enhance the T-cell response to MHC class I peptide vaccines. Forty-three high-risk melanoma patients who were clinically free of disease received 6 vaccinations with MHC class I-restricted tyrosinase peptides alone, with either GM-CSF or KLH or with a combination of both adjuvants. The primary end point was induction of tyrosinase-specific T cells, and serial T-cell monitoring was performed in unstimulated peripheral blood samples before and after the second, fourth and sixth vaccinations by ELISPOT assay. Tyrosinase-specific IFN-gamma-producing T cells were detected as early as 2 weeks after the second vaccination in 5 of 9 patients vaccinated with tyrosinase peptides in combination with GM-CSF and KLH but not in any patient vaccinated with tyrosinase peptides without adjuvants or in combination with either adjuvant alone. After 6 vaccinations, tyrosinase-specific T cells were found in patients immunized with peptides either without adjuvants (3 of 9 patients) or in combination with the single adjuvant GM-CSF (4 of 9 patients) but not with KLH (0 of 10 patients). Our results suggest that addition of either GM-CSF or KLH as a single adjuvant has little impact on the immunogenicity of tyrosinase peptides. The combined application of GM-CSF and KLH was associated with early induction of T-cell responses. (C) 2003 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 12569574
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  • 2
    Keywords: CANCER ; EXPRESSION ; radiotherapy ; MODEL ; DISEASE ; NON-HODGKINS-LYMPHOMA ; PROFILES ; SIGNATURE ; MicroRNAs ; NERVOUS-SYSTEM LYMPHOMA
    Abstract: Despite improved therapeutic regimens, primary CNS lymphoma (PCNSL) remains a therapeutic challenge. A prognostic classification of PCNSL patients may represent an important step towards optimised patient-adapted therapy. However, only higher age and low Karnofsky Performance Status (KPS) have repeatedly been reported to be associated with shorter overall survival (OS). Here we characterised microRNA (miRNA) fingerprints in the blood of PCNSL patients with short-term survival (STS) versus long-term survival (LTS) to assess their potential as novel prognostic biomarkers. Blood was collected from patients enrolled in the G-PCNSL-SG1 trial, a phase III study for patients with newly diagnosed PCNSL. miRNAs were extracted from the blood and analysed by next generation sequencing. The STS group comprised 20 patients with a median OS of 3 months and was compared to 20 LTS patients with a median OS of 55 months. The cohorts were balanced for age and KPS. Twelve annotated miRNAs were significantly deregulated between the two groups. Among them, miR-151a-5p and miR-151b exhibited the most prominent differences. Importantly, the combination of several miRNA allowed for a good separation between short- and long-term survivors with maximal Area Under Curve (AUC) above 0.75. Besides the known miRNAs we identified putative novel miRNA candidates with potential regulatory influence of PCNSL. Finally, the differential regulation of the most promising candidate miRNAs was confirmed by real-time polymerase chain reaction (PCR) in a validation cohort consisting of 20 STS and LTS patients. In conclusion, peripheral blood miRNA expression patterns hold promise as a prognostic tool in PCNSL patients.
    Type of Publication: Journal article published
    PubMed ID: 25534293
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