Associate Professor UC Davis Davis, California, United States
Disclosure(s):
Amir Kol, DACVP: No financial relationships to disclose
Presentation Description / Summary: Feline Infectious Peritonitis (FIP) is a non-zoonotic, systemic hyper-inflammatory, febrile, and generally fatal viral disease in young kittens that is characterized by systemic pyogranulomatous vasculitis and atrophy of secondary lymphoid tissues that is caused by feline infectious peritonitis virus (FIPV). The nucleoside analog and viral RNA polymerase inhibitor GS-441524 effectively treats naturally occurring FIP in cats. However, GS-441524 monotherapy requires 12 weeks of daily drug administration, and its capacity to support lymphoid tissue and immune restoration was not determined. Mesenchymal stem/stromal cells (MSCs) are somatic multipotent stromal cells with established potent anti-inflammatory and regenerative properties. MSCs secrete trophic factors to aid in the regeneration and repair of damaged tissue. Thus, MSC therapy provides a powerful candidate treatment strategy for FIP-infected cats. We hypothesized that a combined GS-441524-MSC therapy is safe, decreases systemic inflammation, rejuvenates T cell exhaustion, and enhances specific anti-FIPV immunity in cats with FIP. We have successfully completed a clinical trial in ten cats with naturally occurring effusive FIP. The trial was administered by the Veterinary Center for Clinical Trials (VCCT) at the UC Davis, Veterinary Medical Teaching Hospital (VMTH). Cats were randomized into a GS-441524-only treatment (n=5) or a combined GS-441524 and 2 intravenous allogeneic MSC infusions (n=5). Samples (PBMCs, plasma, effusion, and mesenteric lymph node aspirates) were collected and preserved for batch analysis. Clinical and basic hematology data were recorded during each visit. Feline-specific flow cytometric panels to interrogate lymphocyte subsets and cytokine production were optimized and analyzed on PBMC samples. Serum concentrations of a battery of cytokines and chemokines were measured via a commercially available feline-specific multiplex immunoassay. We also successfully sequenced the entire transcriptome of individual mesenteric lymph node cells (n=49,064) that were collected from 10 cats prior to treatment and at the end of the trial after the successful completion of the therapeutic protocol. I will share our clinical, hematologic, virologic and immunologic data during this session.
Learner Outcomes: The learners will be able to define mesenchymal stem/stromal cells (MSC) and discuss the rationale for their therapeutic application in cats with FIP. The learners will be able to define T cell exhaustion and mechanisms of lymphocyte death and how these contribute to the pathogenesis of FIP. Finally, the participants will learn about the outcome of a veterinary clinical trial that tested a combined antiviral-SMC therapeutic protocol for FIP and its impact on clinical outcome, hematologic, virology and immunology variables.
Learning Objectives:
Upon completion, participants will be able to define mesenchymal stem/stromal cells (MSC) and discuss the rationale for their therapeutic application in cats with FIP.
Upon completion, participants will be able to define T cell exhaustion and mechanisms of lymphocyte death and how these contribute to the pathogenesis of FIP.
Participants will learn about the outcome of a veterinary clinical trial that tested a combined antiviral-SMC therapeutic protocol for FIP and its impact on clinical outcome, hematologic, virology and immunology variables.
