PDF(Pubmed)
Abstract：
To test the antitumor effect and safety of peptide-based anticancer vaccination in dogs with hemangiosarcoma undergoing the standard of care (SOC; surgery and doxorubicin), canine hemangiosarcoma cells were infected with Salmonella typhi Ty21a to release immunogenic endoplasmic reticulum stress-related peptides into the extracellular milieu via CX43 hemichannels opening. The infected tumor cell secretome constituted the vaccine. Following the SOC, dogs with biologically aggressive hemangiosarcoma were vaccinated a total of five times, once every 3 weeks, and were followed up with serial imaging. A retrospective population of dogs undergoing the SOC alone served as controls. The primary endpoints were the time to progression (TTP) and overall survival (OS), and the secondary endpoints were toxicity and immune responses. A total of 28 dogs were vaccinated along with the SOC, and 32 received only the SOC. A tumor-specific humoral response along with a vaccine-specific T-cell response was observed. Toxicity did not occur. The TTP and OS were significantly longer in vaccinated versus unvaccinated dogs (TTP: 195 vs. 160 days, respectively; p = 0.001; OS: 276 vs. 175 days, respectively; p = 0.002). One-year survival rates were 35.7% and 6.3% for vaccinated and unvaccinated dogs, respectively. In dogs with hemangiosarcoma undergoing the SOC, the addition of a peptide-based vaccine increased the TTP and OS, while maintaining a safe profile. Moreover, vaccinated dogs developed a tumor-specific response, supporting the feasibility of future phase three studies.
摘要：
为了测试基于肽的抗癌疫苗在接受标准护理（SOC；手术和阿霉素）的血管肉瘤犬中的抗肿瘤效果和安全性，犬血管肉瘤细胞感染伤寒沙门氏菌Ty21a，通过CX43半通道开放将免疫原性内质网应激相关肽释放到细胞外环境中。感染的肿瘤细胞分泌组构成疫苗。在SOC之后，对具有生物学侵袭性血管肉瘤的狗总共接种了五次疫苗，每3周一次,并进行了连续成像随访。仅接受SOC的狗的回顾性群体作为对照。主要终点是进展时间（TTP）和总生存期（OS），次要终点是毒性和免疫反应。共有28只狗与SOC一起接种了疫苗，32只收到SOC。观察到肿瘤特异性体液应答以及疫苗特异性T细胞应答。没有发生毒性。与未接种疫苗的狗相比，接种疫苗的狗的TTP和OS明显更长(TTP：195vs.160天,分别为；p=0.001；OS：276vs.175天,分别为；p=0.002)。接种和未接种疫苗的狗一年生存率分别为35.7%和6.3%,分别。在患有血管肉瘤的狗中，添加基于肽的疫苗增加了TTP和OS，同时保持安全的个人资料。此外，接种疫苗的狗产生了肿瘤特异性反应，支持未来第三阶段研究的可行性。
