文章：

一项针对接受手术和化疗的侵袭性血管肉瘤犬的二期、单臂、开放标签临床试验：基于肽的辅助疫苗接种研究

A Phase 2, Single-Arm, Open-Label Clinical Trial on Adjuvant Peptide-Based Vaccination in Dogs with Aggressive Hemangiosarcoma Undergoing Surgery and Chemotherapy

原文发布日期：22 August 2023

DOI: 10.3390/cancers15174209

类型: Article

开放获取: 是

英文摘要：

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 withSalmonella typhiTy21a 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.

摘要翻译： 

为测试基于多肽的抗癌疫苗在接受标准治疗（手术与多柔比星）的犬血管肉瘤中的抗肿瘤效果及安全性，本研究通过伤寒沙门氏菌Ty21a感染犬血管肉瘤细胞，促使细胞通过CX43半通道开放向胞外释放内质网应激相关免疫原性多肽。感染后的肿瘤细胞分泌组构成疫苗制剂。在接受标准治疗后，具有生物学侵袭性的血管肉瘤患犬共接种五次疫苗，每三周一次，并通过系列影像学检查进行随访。以仅接受标准治疗的回顾性犬群作为对照组。主要终点为疾病进展时间与总生存期，次要终点为毒性反应及免疫应答。共28只犬在标准治疗基础上接种疫苗，32只犬仅接受标准治疗。研究观察到肿瘤特异性体液免疫应答及疫苗特异性T细胞反应，未出现毒性反应。接种疫苗犬的疾病进展时间与总生存期均显著长于未接种组（疾病进展时间：195天对160天，p=0.001；总生存期：276天对175天，p=0.002）。接种组与未接种组的一年生存率分别为35.7%和6.3%。研究表明，在接受标准治疗的血管肉瘤患犬中，联合应用多肽疫苗可显著延长疾病进展时间与总生存期，且安全性良好。此外，接种疫苗犬产生了肿瘤特异性免疫应答，这为未来开展三期临床研究提供了可行性依据。

原文链接：

A Phase 2, Single-Arm, Open-Label Clinical Trial on Adjuvant Peptide-Based Vaccination in Dogs with Aggressive Hemangiosarcoma Undergoing Surgery and Chemotherapy