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

Author:

Engbersen Diederik J. M.1,van Beijnum Judy R.12ORCID,Roos Arno3,van Beelen Marit3,de Haan Jan David2,Grinwis Guy C. M.4ORCID,Schalken Jack A.5,Witjes J. Alfred5,Griffioen Arjan W.12ORCID,Huijbers Elisabeth J. M.12ORCID

Affiliation:

1. CimCure BV, 1081 HV Amsterdam, The Netherlands

2. Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands

3. Veterinary Referral Center Korte Akkeren, 2802 LA Gouda, The Netherlands

4. Veterinary Pathology Diagnostic Centre, Department of Biomedical Health Sciences, Faculty of Veterinary Medicine, Utrecht University, 3584 TD Utrecht, The Netherlands

5. Department of Urology, Radboud University Medical Center, 6525 GA Nijmegen, The Netherlands

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.

Funder

Dutch Cancer Society

Publisher

MDPI AG

Subject

Cancer Research,Oncology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Extracellular vimentin as a modulator of the immune response and an important player during infectious diseases;Immunology & Cell Biology;2024-01-11

2. Cancer Immunotherapy;Veterinary Clinics of North America: Small Animal Practice;2023-12

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