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

Diederik J. M. Engbersen, Judy R. van Beijnum, Arno Roos, Marit van Beelen, Jan David de Haan, Guy C. M. Grinwis, Jack A. Schalken, J. Alfred Witjes, Arjan W. Griffioen*, Elisabeth J. M. Huijbers

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Article number3958
Number of pages14
JournalCancers
Volume15
Issue number15
DOIs
Publication statusPublished - 3 Aug 2023

Keywords

  • angiogenesis
  • antiangiogenic therapy
  • bladder cancer
  • immunotherapy
  • tumor vascular marker
  • vaccination
  • vimentin

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