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Monoclonal antibodies (mAbs) have come to dominate the biologics market in human cancer therapy. Nevertheless, in veterinary medicine, very few clinical trials have been initiated using this form of therapy. Some of the advantages of mAb therapeutics over conventional drugs are high specificity, precise mode of action and long half-life, which favour infrequent dosing of the antibody. Further advancement in the field of biomedical sciences has led to the production of different forms of antibodies, such as single chain antibody fragment, Fab, bi-specific antibodies and drug conjugates for use in diagnostic and therapeutic purposes. This review describes the potential for mAbs in veterinary oncology in supporting both diagnosis and therapy of cancer. The technical and financial hurdles to facilitate clinical acceptance of mAbs are explored and insights into novel technologies and targets that could support more rapid clinical development are offered., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Canine inflammatory mammary cancer (IMC) and its human counterpart, inflammatory breast cancer, are extremely aggressive types of cancer. Our aim was to characterize immunohistochemical expression of C-C chemokine receptor 2, colony stimulating factor 1 receptor and metalloproteinase-9 in canine IMC versus non-IMC and to analyze associations with clinicopathological variables., Materials and Methods: Immunohistochemical staining of CCR2, CSF1R and MMP9 was performed in a series of 25 IMC and 15 non-IMC tumors., Results: No differences in the expression of these biomarkers between IMC and non-IMC were observed. Distinct nuclear subcellular expression of CCR2 was observed in IMC (p<0.001). For IMC, higher CCR2 expression was associated with increased nuclear grade (p=0.037), and higher neoplastic MMP9 expression was associated with fewer mitoses (p=0.022), higher nuclear grade (p=0.047) and increased CSF1R expression (p=0.025)., Conclusion: Expression of CCR2, CSF1R and MMP9 in canine IMC could contribute to increased nuclear pleomorphism, but the biological mechanisms involved warrant further investigation., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Advances in biotechnology have enabled the collection of an immeasurable amount of information from genomic, transcriptomic, metabolomic and proteomic studies of tumours within their microenvironments. The dissection of cytokine and chemokine networks has provided new clues to the interactions between cancer cells and their surrounding inflammatory landscape. To bridge the gap between chronic inflammation and cancer, dynamic participants in the tumour microenvironment have been identified, including tumour-associated macrophages (TAMs) and regulatory T cells (Tregs). Both of these cell types are notable for their ability to cause immunosuppressive conditions and support the evasion of tumour immune surveillance. It is clear now that the tumour-promoting inflammatory environment has to be included as one of the major cancer hallmarks. This review explores the recent advances in the understanding of cancer-related inflammation and how this is being applied to comparative oncology studies in humans and domestic species, such as the dog., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Canine mammary carcinoma is the most common cancer in female dogs and is often fatal due to the development of distance metastasis. The microenvironment of a tumour often contains abundant infiltrates of macrophages called tumour-associated macrophages (TAMs). TAMs express an activated phenotype, termed M2, which sustains proliferation of cancer cells, and has been correlated with poor clinical outcomes in human cancer patients. Cancer cells themselves have been implicated in stimulating the conversion of macrophages to a TAM with an M2 phenotype. This process has yet to be fully elucidated. Here we investigate the interplay between cancer cells and macrophages in the context of canine mammary carcinoma., Results: We show that cancer cells inhibit lipopolysaccharide (LPS)-induced macrophage activation. Further, we show that macrophage associated proteins, colony-stimulating factor (CSF)-1 and C-C motif ligand (CCL)-2, stimulate macrophages and are responsible for the effects of cancer cells on macrophages. We suggest the existence of a feedback loop between macrophages and cancer cells; while cancer cells influence the phenotype of the TAMs through CSF-1 and CCL2, the macrophages induce canine mammary cancer cells to upregulate their own expression of the receptors for CSF-1 and CCL2 and increase the cancer cellular metabolic activity. However, these cytokines in isolation induce a phenotypic state in macrophages that is between M1 and M2 phenotypes., Conclusions: Overall, our results demonstrate the extent to which canine mammary carcinoma cells influence the macrophage phenotype and the relevance of a feedback loop between these cells, involving CSF-1 and CCL2 as important mediators.

Prion diseases involve the conversion of the endogenous cellular prion protein, PrP(C), into a misfolded infectious isoform, PrP(Sc). Several functions have been attributed to PrP(C), and its role has also been investigated in the olfactory system. PrP(C) is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp(-/-) mice showed impaired behavior in olfactory tests. Given the high PrP(C) expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrP(C)-binding partners. Ten different putative PrP(C) ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrP(C) with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrP(C)-Stub1 interaction are under investigation. The PrP(C)-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrP(C) is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein.

Avian pathogenic Escherichia coli is a current problem in the poultry industry, causing mortality and economic losses. This paper evaluates the dynamics in immune response after the use of spray vaccination against E. coli and, thereby, seeks to understand how the vaccine can provide protection. During the early stages of response to vaccination the presence of antigen-presenting cells is predominant, but these diminish within the first 7 days after vaccination. The immune correlate of protection of vaccination using the E. coli vaccine Poulvac E. coli (aroA-deficient mutant strain) probably does not depend on the production of circulating antibodies (as assessed through the presence of B lymphocytes) and is linked to the presence of CD4+TCRVbeta1+. These cells act on mucosa tissue stimulating the production of immunoglobulin A. Vaccination stimulated a high state of immunocompetence, as assessed by measurement of several cellular subsets. This state of "immune alertness," however, may be associated with reduced weight gain. The high presence of naive and memory CD8 cells in the vaccinated group at 14 and 21 days postvaccination may indicate greater ability in the future to prevent tissue invasion by E. coli, based on the possibility that these cells will proliferate rapidly to a new stimulus. The simultaneous use of vaccine with the antibiotic ceftiofur sodium interferes with the immune response obtained through vaccination. In combination, the data obtained in this study indicate that the immune response produced by a spray vaccine against E. coli is mainly a cellular response, especially relevant to the sites in contact with the pathogen. It is suggested that there is a strong cell migration to the mucous membranes, where macrophages act first and then lymphocytes take part to protect the host. It is believed that recruited lymphocytes will act in the production of secreted IgA, which probably plays a greater role in the defense when compared with circulating immunoglobulins. The assessment of cellular dynamics by flow cytometry made it possible to elucidate the operation mechanism of the live E. coli vaccine.

Broilers and layer chickens have been intensively selected for production parameters. This selection has affected immune capacity. Consequently, the fine-tuning of immune responses is becoming important for maximum productivity. Flow cytometry is a recurrent technology used for the immunophenotyping of birds. Studies, however, have focused on the mechanism of specific diseases or have used animals whose immunological condition could be biased-by vaccination or environmental stressors, for example. The aim of this study was to evaluate the immune status of specific-pathogen-free birds across different age ranges to characterize the natural changes that occur over time. Additionally, specific-pathogen-free chickens were challenged with four infectious agents, allowing identification of the subpopulations of peripheral blood immune cells that are consistently altered under various conditions. Several lymphocyte subsets vary naturally with aging, so the interpretation of results using animals of different age ranges must proceed with care. Parameters such as CD8(+)CD28(-), CD8αα(+), CD4(+)CD8(+), and CD8(+)TCRVβ1(+) have been shown to be valuable in understanding immune changes during disease. The use of these data allows a determination of the consistency of cytometric parameters under various conditions, which should ease the interpretation of immunophenotyping and the future application of cytometric analysis in the poultry industry., (Copyright © 2011 Elsevier B.V. All rights reserved.)