Engbersen Diederik J M, van Beijnum Judy R, Roos Arno, van Beelen Marit, de Haan Jan David, Grinwis Guy C M, Schalken Jack A, Witjes J Alfred, Griffioen Arjan W, Huijbers Elisabeth J M
CimCure BV, 1081 HV Amsterdam, The Netherlands.
Angiogenesis Laboratory, Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, 1081 HV Amsterdam, The Netherlands.
Cancers (Basel). 2023 Aug 3;15(15):3958. doi: 10.3390/cancers15153958.
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 ( < 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.
最近的研究表明，在临床前模型中，靶向细胞外波形蛋白（eVim）是安全有效的。在此，我们报告了CVx1在患有自发性膀胱癌的客户拥有犬中的安全性和有效性，CVx1是一种基于iBoost技术的疫苗，靶向eVim并联合COX-2抑制。这是一项单臂前瞻性1/2期研究，对20只患有自发性尿路上皮癌的客户拥有犬使用CVx1，包括每2周进行4次皮下注射CVx1以诱导抗体滴度，随后每2个月进行维持接种。此外，每天给予美洛昔康抑制环氧化酶（COX）-2。通过抗体滴度、身体状况、腹部超声和胸部X线评估反应。主要终点是抗体滴度的产生以及与接受卡铂和吡罗昔康抑制COX-2的历史对照组相比的总生存期。进行了Kaplan-Meier生存分析。所有犬均产生了针对eVim的抗体。在本研究期间，滴度得到了充分维持。观察到中位总生存期为374天，历史对照组为196天（<0.01）。观察到注射部位有短期1-2级毒性以及接种疫苗前后一些相关的全身症状。未观察到与诱导的抗体反应相关的毒性。本研究的一个局限性是单臂前瞻性设置。CVx1加美洛昔康持续诱导有效的抗体滴度，耐受性良好并显示出生存期延长。所获得的结果值得在人类临床护理中进一步开发。
