Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
Filter
  • DKFZ Publication Database  (3)
  • 1
    Keywords: APOPTOSIS ; THERAPY ; LYMPHOCYTES ; CANCER-IMMUNOTHERAPY ; DONORS ; ANTIGEN SURVIVIN
    Abstract: BACKGROUND: Therapeutic vaccination directed to induce an anti-tumoral T-cell response is a field of extensive investigation in the treatment of melanoma. However, many vaccination trials in melanoma failed to demonstrate a correlation between the vaccine-specific immune response and therapy outcome. This has been mainly attributed to immune escape by antigen loss, rendering us in the need of new vaccination targets. PATIENTS AND METHODS: This phase-II trial investigated a peptide vaccination against survivin, an oncogenic inhibitor-of-apoptosis protein crucial for the survival of tumor cells, in HLA-A1/-A2/-B35-positive patients with treatment-refractory stage-IV metastatic melanoma. The study endpoints were survivin-specific T-cell reactivity (SSTR), safety, response, and survival (OS). RESULTS: Sixty-one patients (ITT) received vaccination therapy using three different regimens. 55 patients (PP) were evaluable for response and survival, and 41/55 for SSTR. Patients achieving progression arrest (CR + PR + SD) more often showed SSTRs than patients with disease progression (p = 0.0008). Patients presenting SSTRs revealed a prolonged OS (median 19.6 vs. 8.6 months; p = 0.0077); multivariate analysis demonstrated SSTR as an independent predictor of survival (p = 0.013). The induction of SSTRs was associated with gender (female vs. male; p = 0.014) and disease stage (M1a/b vs. M1c; p = 0.010), but not with patient age, HLA type, performance status, or vaccination regimen. CONCLUSION: Survivin-specific T-cell reactivities strongly correlate with tumor response and patient survival, indicating that vaccination with survivin-derived peptides is a promising treatment strategy in melanoma.
    Type of Publication: Journal article published
    PubMed ID: 22565484
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: PEPTIDE ; CANCER ; CELLS ; BLOOD ; CELL ; CLINICAL-TRIAL ; COMBINATION ; NEW-YORK ; DISTINCT ; SAMPLE ; SAMPLES ; RESPONSES ; BASE ; CD8(+) T-CELLS ; T cell ; T cells ; T-CELL ; T-CELLS ; ASSOCIATION ; TRIAL ; TRIALS ; IDENTIFICATION ; ASSAY ; NUMBER ; CLINICAL-TRIALS ; COUNTRIES ; MELANOMA ; LYMPHOCYTES ; VARIABILITY ; PEPTIDES ; NETHERLANDS ; CD8(+) ; ELISPOT ; IMMUNOTHERAPY ; T-LYMPHOCYTES ; T lymphocyte ; sensitivity ; PERIPHERAL-BLOOD ; PROJECT ; INTERFERON-GAMMA ; tetramer ; T lymphocytes ; GUIDELINES ; HETEROGENEITY ; CANCER VACCINES ; ONCOLOGY ; monitoring ; INCREASE ; analysis ; methods ; ASSAYS ; PHASE ; technique ; USA ; RECOMMENDATIONS ; STANDARDIZATION ; VARIABLES ; immunology ; INCREASES ; clinical trial ; CELL RESPONSES ; IMPORTANT DETERMINANT ; CD4+T-CELL IMMUNITY ; CYTOKINE FLOW-CYTOMETRY ; GAMMA ELISPOT ASSAYS ; Interlaboratory testing
    Abstract: The interpretation of the results obtained from immunomonitoring of clinical trials is a difficult task due to the variety of methods and protocols available to detect vaccine-specific T-cell responses. This heterogeneity as well as the lack of standards has led to significant scepticism towards published results. In February 2005, a working group was therefore founded under the aegis of the Association for Immunotherapy of Cancer ("CIMT") in order to compare techniques and protocols applied for the enumeration of antigen-specific T-cell responses. Here we present the results from two consecutive phases of an international inter-laboratory testing project referred to as the "CIMT monitoring panel". A total of 13 centers from six European countries participated in the study in which pre-tested PBMC samples, synthetic peptides and PE-conjugated HLA-tetramers were prepared centrally and distributed to participants. All were asked to determine the number of antigen-specific T-cells in each sample using tetramer staining and one functional assay. The results of the first testing round revealed that the total number of cells analyzed was the most important determinant for the sensitive detection of antigen-specific CD8(+) T-cells by tetramer staining. Analysis by ELISPOT was influenced by a combination of cell number and a resting phase after thawing of peripheral blood mononuclear cells. Therefore, the experiments were repeated in a second phase but now the participants were asked to change their protocols according to the new guidelines distilled from the results of the first phase. The recommendations improved the number of antigen-specific T-cell responses that were detected and decreased the variability between the laboratories. We conclude that a two-step approach in inter-laboratory testing allows the identification of distinct variables that influence the sensitivity of different T-cell assays and to formally show that a defined correction to the protocols successfully increases the sensitivity and reduces the inter-center variability. Such "two-step" inter-laboratory projects could define rational bases for accepted international guidelines and thereby lead to the harmonization of the techniques used for immune monitoring
    Type of Publication: Journal article published
    PubMed ID: 17721783
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Abstract: Regular exercise reduces the risk of cancer and disease recurrence. Yet the mechanisms behind this protection remain to be elucidated. In this study, tumor-bearing mice randomized to voluntary wheel running showed over 60% reduction in tumor incidence and growth across five different tumor models. Microarray analysis revealed training-induced upregulation of pathways associated with immune function. NK cell infiltration was significantly increased in tumors from running mice, whereas depletion of NK cells enhanced tumor growth and blunted the beneficial effects of exercise. Mechanistic analyses showed that NK cells were mobilized by epinephrine, and blockade of beta-adrenergic signaling blunted training-dependent tumor inhibition. Moreover, epinephrine induced a selective mobilization of IL-6-sensitive NK cells, and IL-6-blocking antibodies blunted training-induced tumor suppression, intratumoral NK cell infiltration, and NK cell activation. Together, these results link exercise, epinephrine, and IL-6 to NK cell mobilization and redistribution, and ultimately to control of tumor growth.
    Type of Publication: Journal article published
    PubMed ID: 26895752
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...