Cytokine Expression of Activated T cells in Dogs Undergoing Adoptive T cell therapy for Osteosarcoma

Abstract: Background - Immunotherapeutics have revolutionized how cancer may be treated by conditioning the host immune system to generate an anti-cancer response. These therapies are becoming more available to veterinary practitioners. Here we examine blood cytokine expression sampled from dogs undergoing vaccine enhanced adoptive T cell therapy (VACT).

Hypothesis/Objectives - T cells conditioned in vivo to cancer antigens will, after ex vivo activation and expansion, release large amounts of proinflammatory cytokines. T cells conditioned to cancer antigens, but not activated, will have lesser cytokine expression in the presence of cancer cells.

Animals - 4 privately owned dogs undergoing VACT for appendicular osteosarcoma.

Methods - Dogs underwent VACT consisting of 3 weekly autologous cancer cell vaccinations, T cell harvest via apheresis, ex-vivo T cell activation and reinfusion. Samples were collected at three timepoints: prior to vaccination, two weeks post-vaccination, and post-T cell activation.

Results - High levels of proinflammatory cytokines (e.g., IFN-gamma, IL-6, TNF-alpha) were expressed by post-activation T cells in the presence of host tumor cells. Whereas naïve T cells and post-vaccination T cells did not express high levels of these cytokines in the presence of host tumor cells.

Conclusions and clinical importance - Host T cells conditioned to target cancer antigens via autologous cancer cell vaccination and then ex vivo activated and expanded can actively mount an anti-cancer immune response. In the presence of the target cancer cells, these activated T cells will initiate an immune response via upregulation of cytokine expression.