Leg problems are highly prevalent in modern broiler production and provision of environmental enrichment could be a strategy to improve leg health. Different types of environmental enrichment have undergone evaluation. Our objective was to conduct a systematic review of the effect of environmental enrichment on leg health in broiler chickens. The evaluation of leg health included measures of the entire leg and foot, and behavioural, pathological and physical measures. Six types of environmental enrichment were selected for inclusion: light programme, intensity of light, stocking density, perches, straw bales and separation of resources. For each type, a systematic literature search was performed. The review included 62 studies; 56 randomised trials and six cross-sectional studies. An assessment of the methodological quality of all 56 randomised trials was performed with some reporting deficits regarding occurrence of blinding, randomisation and reliability of measures. Provision of perches and increased intensity of light only displayed limited effectiveness in improving leg health and both mainly affected contact dermatitis. In contrast, there was evidence that a lowered stocking density and a dark/light schedule could improve leg health. Few studies have been carried out on the effect of straw bales and separation of resources. The few studies done have, however, shown that both types of enrichment can be effective in improving leg health. In conclusion, identifying and providing the optimal types of enrichment for broilers will reduce leg problems and increase mobility, thereby improving the welfare of the birds.
BackgroundMany cancers acquire mechanisms to evade immunosurveillance by activating immune checkpoint pathways, which suppress the antitumor immune responses. Monoclonal antibodies (ab’s) targeting immune checkpoints, such as CTLA-4 and PD-1, have shown excellent results in several cancers and are currently being investigated in clinical trials for various malignancies. The clinically tested a-CTLA-4 (Ipilimumab) and a-PD-1 (Nivolumab and Pembrolizumab) ab’s are fully human or humanized ab’s, respectively. However, most studies conducted in mice utilize a xenogeneic a-PD-1 ab originating from rat, IgG2a RMP1-14 clone. This has been proposed to cause adverse effects in the commonly used 4T1 mammary carcinoma model of triple negative breast cancer (TNBC). Repeated administration of xenogeneic a-PD-1 ab’s in this model results in fatal hypersensitivity reactions in tumor bearing mice, and unlike human TNBC, the 4T1 cell line is generally poorly responsive to immune checkpoint inhibitors. Recently, a semi-syngeneic recombinant a-PD-1 ab has been developed by transferring the variable regions of RMP1-14 onto a murine IgG1e3 constant region.Materials and MethodsTesting xenogeneic and semi-syngeneic a-PD-1 ab with and without a-CTLA-4 ab in BALB/c mice carrying 4T1 luciferase positive tumors.ResultsIn this study, we compared a semi-syngeneic recombinant a-PD-1 ab to the original xenogeneic RMP1-14 clone for treatment of luciferase positive 4T1 carcinomas. Surprisingly, the semi-syngeneic a-PD-1 ab was not able to circumvent the fatal hypersensitivity reactions. Still, the combination therapy of a-CTLA-4 and the semi-syngeneic a-PD-1 ab significantly reduced tumor volume in 4T1-luciferase tumor bearing mice compared to isotype control-treated mice already from day 16 post tumor inoculation (day 8 post treatment-initiation). In contrast, xenogeneic a-PD-1/a-CTLA-4 treated mice did not show significant difference from the control group until 24 days post tumor inoculation and never to the same degree. Furthermore, analysis of the T cell responses towards the murine tumor-associated antigen AH-1, revealed that treatment with syngeneic a-PD-1/a-CTLA-4 ab gave a significantly stronger CD8+ T cell response over both control mice and mice treated with xenogeneic a-PD-1/a-CTLA-4 ab.ConclusionsThese studies indicate that the semi-syngeneic a-PD-1 IgG1e3 ab might be a more efficient and translatable a-PD-1 ab for preclinical in vivo studies, which is important for the future investigation of immune checkpoint inhibitor therapy.Disclosure InformationI. Skandorff Pedersen: A. Employment (full or part-time); Significant; InProTher Aps. K. Orfin: A. Employment (full or part-time); Significant; InProTher Aps. K.N. Nielsen: A. Employment (full or part-time); Significant; InProTher Aps. P.J. Holst: A. Employment (full or part-time); Significant; InProTher Aps. E. Ownership Interest (stock, stock options, patent or other intellectual property); Significant; InProTher Aps.
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