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.
最近研究表明，靶向细胞外波形蛋白（eVim）在临床前模型中安全有效。本文报告了基于iBoost技术、靶向eVim的CVx1疫苗联合COX-2抑制疗法在自发膀胱癌客户饲养犬中的安全性与疗效。这是一项单臂前瞻性1/2期研究，对20只自发性膀胱尿路上皮癌（UC）客户饲养犬进行CVx1治疗：首先每两周皮下接种一次CVx1疫苗（共四次）以诱导抗体滴度，随后每两个月接种一次维持疫苗。同时每日给予美洛昔康进行环氧化酶（COX）-2抑制。通过抗体滴度、体格检查、腹部超声和胸部X光评估疗效。主要终点包括抗体滴度发展情况，以及与接受卡铂联合吡罗昔康COX-2抑制的历史对照组相比的总生存期。研究采用卡普兰-迈耶生存分析法。所有犬均产生抗eVim抗体，研究期间抗体滴度保持稳定。中位总生存期为374天，历史对照组为196天（p<0.01）。观察到注射部位出现1-2级短期毒性及疫苗接种期间相关全身症状，但未发现与诱导抗体反应相关的毒性。本研究受限于单臂前瞻性设计。CVx1联合美洛昔康能持续诱导有效抗体滴度，耐受性良好，并可延长生存期。该成果值得进一步开发应用于人类临床治疗。
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