Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs

SIMPLE SUMMARY: In this study, we investigated the safety and usefulness of treatment of dog patients with spontaneous bladder cancer with the CVx1 vaccine. The vaccine is directed against a specific protein, named extracellular vimentin, excreted by the tumor vasculature. Twenty dogs diagnosed at the veterinary clinic with bladder cancer were treated with the CVx1 vaccine in combination with the non-steroidal anti-inflammatory drug (NSAID) meloxicam. All dogs responded to the treatment and developed an immune response towards the tumor vasculature. After treatment with the CVx1 vaccine plus meloxicam, the survival was almost doubled (374 days) compared to the historical control group (196 days) treated with the chemotherapy carboplatin in combination with the NSAID piroxicam. Treatment with the CVx1 vaccine combined with meloxicam was safe and well tolerated. Our results justify further development of the CVx1 vaccine for the treatment of human patients in the clinic. ABSTRACT: It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan–Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1–2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care.