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Veterinary immunology and immunopathology2008; 128(1-3); 16-23; doi: 10.1016/j.vetimm.2008.10.317

Clinical application of dendritic cells and interleukin-2 and tools to study activated T cells in horses–first results and implications for quality control.

Abstract: Dendritic cells (DCs) are antigen-presenting cells, which are well known for their capacity to stimulate immunity. The ex vivo generation of myeloid DC from monocytes has facilitated the development of DC-vaccination protocols which have been extensively evaluated in tumour immunology and are regarded by some as a gold mine for clinical research. However, there is a considerable amount of work required to overcome the potential risks associated with such therapy. It is therefore mandatory to characterize the system to be applied and to study the reactions, particularly at the level of T cell responses. The first objective of the current study was to test if tumour lysates loaded autologous DC or recombinant human IL-2 are well tolerated in horses and performed an exploratory phase I study on equine sarcoids and squamous cell carcinomas. We consequently intended to establish a robust protocol for the magnetic separation of monocytes such as in use in human clinical studies. Finally we intended to address the limits in the reagents to study equine T cell based immune reactions, and analysed markers for CD25 and FoxP3. The data showed that local application of DC or IL-2 did not cause side effects. Additionally our data show that a polyclonal approach to detect antigens such as CD25 might be successful, where mAbs are not available. Our data also demonstrate that the mAb FJK16s, which has been used successfully in rodents, humans, and dogs, can also be applied in horses. We finally wish to share our concerns regarding quality control for clinical studies and encourage multi-central studies such as in human medicine to ensure that progress along established standards is made for the benefit of veterinary medicine.
Publication Date: 2008-10-22 PubMed ID: 19056130DOI: 10.1016/j.vetimm.2008.10.317Google Scholar: Lookup
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  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article investigates how an immune response can be fostered in horses through the application of dendritic cells and interleukin-2. It explores how to create an effective protocol involving these agents, monitoring T cell responses, and identifying potential quality control concerns in clinical studies.

Understanding Dendritic Cells and Interleukin-2

  • Dendritic Cells (DCs) are a type of white blood cells that present antigens to other immune cells, creating a response. Using these cells in ex vivo studies can support the development of vaccination protocols, particularly for tumour immunology.
  • Interleukin-2 (IL-2) is a type of cytokine signaling molecule in the immune system. It regulates white blood cell activity, crucial for a body’s fight against disease.

Study Objectives

  • The research had multiple objectives. Firstly, it aimed to test whether autologous DC or recombinant human IL-2 loaded with tumor lysates were well tolerated in horses. Specifically, these treatments were applied to equine sarcoids and squamous cell carcinomas during an exploratory phase I study.
  • The research also aimed to create a robust protocol for the magnetic separation of monocytes, a technique often used in human clinical studies.
  • Finally, the researchers wanted to highlight the limitations in reagents used to study T cell based immune reactions in horses, particularly those related to CD25 and FoxP3 markers.

Findings and Implications

  • The study found that local application of DC or IL-2 resulted in no side effects, indicating its potential tolerance in horses.
  • The research also detected that a polyclonal approach to identify antigens, like CD25, could succeed when monoclonal antibodies (mAbs) are not available.
  • Experiments showed that mAb FJK16s, used previously in rodents, humans, and dogs, can also be used in horses, broadening its potential use in clinical practices.
  • The study authors noted that quality control is crucial in these clinical trials. They suggested adopting multicenter studies, as done in human medicine, to adhere to established standards and benefit veterinary medicine.

Cite This Article

APA
Steinbach F, Bischoff S, Freund H, Metzner-Flemisch S, Ibrahim S, Walter J, Wilke I, Mauel S. (2008). Clinical application of dendritic cells and interleukin-2 and tools to study activated T cells in horses–first results and implications for quality control. Vet Immunol Immunopathol, 128(1-3), 16-23. https://doi.org/10.1016/j.vetimm.2008.10.317

Publication

ISSN: 0165-2427
NlmUniqueID: 8002006
Country: Netherlands
Language: English
Volume: 128
Issue: 1-3
Pages: 16-23

Researcher Affiliations

Steinbach, Falko
  • Virology Department, Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK. f.steinbach@vla.defra.gsi.gov.uk
Bischoff, Sabine
    Freund, Hannah
      Metzner-Flemisch, Simone
        Ibrahim, Sherif
          Walter, Jakob
            Wilke, Ingo
              Mauel, Susanne

                MeSH Terms

                • Animals
                • Biomarkers
                • Dendritic Cells / metabolism
                • Dendritic Cells / physiology
                • Forkhead Transcription Factors / metabolism
                • Horse Diseases / immunology
                • Horse Diseases / therapy
                • Horses
                • Humans
                • Interleukin-2 / pharmacology
                • Interleukin-2 Receptor alpha Subunit / metabolism
                • Lymphocyte Activation / physiology
                • Quality Control
                • T-Lymphocytes / physiology

                Citations

                This article has been cited 7 times.
                1. Moyo NA, Westcott D, Simmonds R, Steinbach F. Equine Arteritis Virus in Monocytic Cells Suppresses Differentiation and Function of Dendritic Cells. Viruses 2023 Jan 16;15(1).
                  doi: 10.3390/v15010255pubmed: 36680295google scholar: lookup
                2. Bowlby CM, Purmessur D, Durgam SS. Equine peripheral blood CD14(+) monocyte-derived macrophage in-vitro characteristics after GM-CSF pretreatment and LPS+IFN-γ or IL-4+IL-10 differentiation. Vet Immunol Immunopathol 2023 Jan;255:110534.
                  doi: 10.1016/j.vetimm.2022.110534pubmed: 36502640google scholar: lookup
                3. Saba C, Eggleston R, Parks A, Peroni J, Sjoberg E, Rice S, Tyma J, Williams J, Grosenbaugh D, Leard AT. ALVAC-fIL2, a feline interleukin-2 immunomodulator, as a treatment for sarcoids in horses: A pilot study. J Vet Intern Med 2022 May;36(3):1179-1184.
                  doi: 10.1111/jvim.16425pubmed: 35416353google scholar: lookup
                4. Ziegler A, Everett H, Hamza E, Garbani M, Gerber V, Marti E, Steinbach F. Equine dendritic cells generated with horse serum have enhanced functionality in comparison to dendritic cells generated with fetal bovine serum. BMC Vet Res 2016 Nov 15;12(1):254.
                  doi: 10.1186/s12917-016-0880-8pubmed: 27846835google scholar: lookup
                5. Moyo NA, Marchi E, Steinbach F. Differentiation and activation of equine monocyte-derived dendritic cells are not correlated with CD206 or CD83 expression. Immunology 2013 Aug;139(4):472-83.
                  doi: 10.1111/imm.12094pubmed: 23461413google scholar: lookup
                6. Cavatorta DJ, Erb HN, Felippe MJ. Activation-induced FoxP3 expression regulates cytokine production in conventional T cells stimulated with autologous dendritic cells. Clin Vaccine Immunol 2012 Oct;19(10):1583-92.
                  doi: 10.1128/CVI.00308-12pubmed: 22855393google scholar: lookup
                7. Hamza E, Gerber V, Steinbach F, Marti E. Equine CD4(+) CD25(high) T cells exhibit regulatory activity by close contact and cytokine-dependent mechanisms in vitro. Immunology 2011 Nov;134(3):292-304.