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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: IRRADIATION ; radiotherapy ; tumor ; Germany ; THERAPY ; TOXICITY ; CT ; imaging ; INFORMATION ; SYSTEM ; TOOL ; VOLUME ; RISK ; TUMORS ; PATIENT ; MARKER ; REDUCTION ; CONTRAST ; MR ; MRI ; treatment ; TRIAL ; RADIATION-THERAPY ; STEREOTACTIC RADIOSURGERY ; MELANOMA ; SAFETY ; treatment planning ; RECONSTRUCTION ; ultrasound ; proton therapy ; INTEGRATION ; uveal melanoma ; SIZE ; GAMMA-KNIFE ; GEOMETRY ; EYE ; BEAM RADIOTHERAPY ; BRACHYTHERAPY ; CHOROIDAL MELANOMA ; EYEPLAN ; INTRAOCULAR TUMORS ; OCTOPUS ; SURFACE COIL
    Abstract: Background and Purpose: Proton therapy for uveal melanoma provides high-conformal dose application to the target volume and, thus, an optimal saving of the organs at risk nearby. Treatment planning is done with the model-based treatment-planning system EYEPLAN. Tumor reconstruction is based only on a fundus composite, which often leads to an overestimation of the clinical target volume (CTV). The purpose was to exploit MRI on trial in a proton therapy-planning system by using the novel image-based treatment-planning system OCTOPUS. Patients and Methods: Ten patients with uveal melanomas received both a high-resolution planning CT and MRI of the eye. MR examinations were made with an eye coil. EYEPLAN requires eye geometry data for modeling, and tantalum marker clips for submillimeter positioning and additional information from ultrasound and 3-D imaging. By contrast, OCTOPUS provides the full integration of 3-D imaging (e.g., CT, MRI). CTVs were delineated in each slice. For all patients, CTVs (EYEPLAN vs. OCTOPUS) were compared intraindividually. Results: OCTOPUS planning led to a mean reduction of the target volume by a factor of 1.7 (T1-weighted [T1w]) and 2.2 (T2w) without compromising safety. The corresponding field size could be scaled down on average by a factor of 1.2 (T1w) and 1.4 (T2w), respectively. Conclusion: Compared with the conventional EYEPLAN, MRI-based treatment planning of ocular tumors with OCTOPUS could be a powerful tool for reducing the CTV and, consequently, the treatment volume and the field size. This might be translated into a better patient compliance during treatment and a decreased late toxicity
    Type of Publication: Journal article published
    PubMed ID: 16826358
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