Eignung unterschiedlicher Herkünfte für die ökologische Haltung von Masthähnchen - Feldprüfung

Die Eignung unterschiedlich langsam wachsender Herkünfte für die ökologische Hühnermast wurde unter dem Aspekt der Tiergesundheit und des Verhaltens untersucht. In zwei Durchgängen wurden insgesamt 5721 Tiere der Herkunft Hubbard JA 757, dreier weiterer, langsamer wachsende Herkünfte und zweier Rasseherkünfte auf je acht Betrieben in je zwei bis vier Gruppen von 27 bis 565 Tieren gemästet. Die mittleren täglichen Zunahmen lagen zwischen 18,3±3,3 g (Rassetiere) und 40,6±6,9 g (Hubbard), die Verluste bei 2,3 ± 2,6 %. Über alle Herkünfte wurden im Mittel weniger als 5 % lahme Tiere festgestellt. Veränderungen der Fußballen (47,7 %), Läsionen der Fersenhöcker (7,3 %), Verschmutzungen des Brustgefieders (67,5 %) und Läsionen der Brusthaut (7,5 %) konnten bei allen Herkünften außer den Rassetieren beobachtet werden. Auch Hautverletzungen kamen bei den Hybriden häufiger vor (37,8 %) als bei den Rassetieren (1,4 %). Unter Einbeziehung der Daten des Projekts 06OE217, bei dem dieselben Herkünfte auf einem Versuchsbetrieb eingestallt waren, wurden signifikante Herkunftsunterschiede gefunden (p<0,0001), wobei die Rassetiere und die langsamer wachsenden Herkünfte meist niedrigere Schadensprävalenzen aufwiesen als die Herkunft Hubbard. Die zusätzlich auf dem Versuchbetrieb gehaltene Herkunft Ross wies meist nochmals weniger Tiere ohne Schäden auf. Je höher die tägliche Zunahme, desto mehr Tiere wiesen Schäden auf (p<0,0001). Das Gewicht und die Brustbreite beeinflussten den Gesundheitszustand der Tiere ebenfalls negativ. In Verhaltenstests waren keine Unterschiede zwischen den Hybridherkünften in ihrer Furchtsamkeit gegenüber einem neuen Objekt oder einem Menschen festzustellen. Vor dem Hintergrund des engen Zusammenhangs zwischen Wachstumsgeschwindigkeit, Brustbreite und dem Auftreten von Gesundheitsproblemen, sollte das Auftreten von Schäden regelmäßig erfasst und stärker diskutiert werden, welche Niveaus in der ökologischen Hühnermast noch tolerabel sind

TCR-transgenic T cells and YB-1-based oncolytic virotherapy improve survival in a preclinical Ewing sarcoma xenograft mouse model

BackgroundEwing sarcoma (EwS) is an aggressive and highly metastatic bone and soft tissue tumor in pediatric patients and young adults. Cure rates are low when patients present with metastatic or relapsed disease. Therefore, innovative therapy approaches are urgently needed. Cellular- and oncolytic virus-based immunotherapies are on the rise for solid cancers.MethodsHere, we assess the combination of EwS tumor-associated antigen CHM1319-specific TCR-transgenic CD8+ T cells and the YB-1-driven (i.e. E1A13S-deleted) oncolytic adenovirus XVir-N-31 in vitro and in a xenograft mouse model for antitumor activity and immunostimulatory properties.ResultsIn vitro both approaches specifically kill EwS cell lines in a synergistic manner over controls. This effect was confirmed in vivo, with increased survival using the combination therapy. Further in vitro analyses of immunogenic cell death and antigen presentation confirmed immunostimulatory properties of virus-infected EwS tumor cells. As dendritic cell maturation was also increased by XVir-N-31, we observed superior proliferation of CHM1319-specific TCR-transgenic CD8+ T cells only in virus-tested conditions, emphasizing the superior immune-activating potential of XVir-N-31.ConclusionOur data prove synergistic antitumor effects in vitro and superior tumor control in a preclinical xenograft setting. Combination strategies of EwS-redirected T cells and YB-1-driven virotherapy are a highly promising immunotherapeutic approach for EwS and warrant further evaluation in a clinical setting

MHC Class I-Restricted TCR-Transgenic CD4+ T Cells Against STEAP1 Mediate Local Tumor Control of Ewing Sarcoma In Vivo

In this study we report the functional comparison of T cell receptor (TCR)-engineered major histocompatibility complex (MHC) class I-restricted CD4+ versus CD8+ T cells targeting a peptide from six transmembrane epithelial antigen of the prostate 1 (STEAP1) in the context of HLA-A*02:01. STEAP1 is a tumor-associated antigen, which is overexpressed in many cancers, including Ewing sarcoma (EwS). Based on previous observations, we postulated strong antitumor potential of tumor-redirected CD4+ T cells transduced with an HLA class I-restricted TCR against a STEAP1-derived peptide. We compared CD4+ T cell populations to their CD8+ counterparts in vitro using impedance-based xCELLigence and cytokine/granzyme release assays. We further compared antitumor activity of STEAP130-TCR transgenic (tg) CD4+ versus CD8+ T cells in tumor-bearing xenografted Rag2&minus;/&minus;&gamma;c&minus;/&minus; mice. TCR tgCD4+ T cells showed increased cytotoxic features over time with similar functional avidity compared to tgCD8+ cells after 5&ndash;6 weeks of culture. In vivo, local tumor control was equal. Assessing metastatic organotropism of intraveniously (i.v.) injected tumors, only tgCD8+ cells were associated with reduced metastases. In this analysis, EwS-redirected tgCD4+ T cells contribute to local tumor control, but fail to control metastatic outgrowth in a model of xenografted EwS

Ewing Sarcoma-Derived Extracellular Vesicles Impair Dendritic Cell Maturation and Function

Ewing sarcoma (EwS) is an aggressive pediatric cancer of bone and soft tissues characterized by scant T cell infiltration and predominance of immunosuppressive myeloid cells. Given the important roles of extracellular vesicles (EVs) in cancer-host crosstalk, we hypothesized that EVs secreted by EwS tumors target myeloid cells and promote immunosuppressive phenotypes. Here, EVs were purified from EwS and fibroblast cell lines and exhibited characteristics of small EVs, including size (100–170 nm) and exosome markers CD63, CD81, and TSG101. Treatment of healthy donor-derived CD33+ and CD14+ myeloid cells with EwS EVs but not with fibroblast EVs induced pro-inflammatory cytokine release, including IL-6, IL-8, and TNF. Furthermore, EwS EVs impaired differentiation of these cells towards monocytic-derived dendritic cells (moDCs), as evidenced by reduced expression of co-stimulatory molecules CD80, CD86 and HLA-DR. Whole transcriptome analysis revealed activation of gene expression programs associated with immunosuppressive phenotypes and pro-inflammatory responses. Functionally, moDCs differentiated in the presence of EwS EVs inhibited CD4+ and CD8+ T cell proliferation as well as IFNγ release, while inducing secretion of IL-10 and IL-6. Therefore, EwS EVs may promote a local and systemic pro-inflammatory environment and weaken adaptive immunity by impairing the differentiation and function of antigen-presenting cells.Medicine, Faculty ofNon UBCPathology and Laboratory Medicine, Department ofReviewedFacultyResearche