Clinical application of dendritic cells and interleukin-2 and tools to study activated T cells in horses--first results and implications for quality control.
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.
Steinbach
Falko
F
Virology Department, Veterinary Laboratories Agency (VLA), Woodham Lane, New Haw, Addlestone, Surrey KT15 3NB, UK. f.steinbach@vla.defra.gsi.gov.uk
Bischoff
Sabine
S
Freund
Hannah
H
Metzner-Flemisch
Simone
S
Ibrahim
Sherif
S
Walter
Jakob
J
Wilke
Ingo
I
Mauel
Susanne
S
D000818:Animals; D015415:Biomarkers; D003713:Dendritic Cells / Q000378:metabolism* / Q000502:physiology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006734:Horse Diseases / Q000276:immunology* / Q000628:therapy; D006736:Horses; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D011786:Quality Control; D013601:T-Lymphocytes / Q000502:physiology*
D015415:Biomarkers; D051858:Forkhead Transcription Factors; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit