Institute of Cytology of the Russian Academy of Sciences, Russian Federation ; AL Polenov Russian Research Scientific Institute of Neurosurgery, Russian Federation.
AL Polenov Russian Research Scientific Institute of Neurosurgery, Russian Federation.
Onco Targets Ther. 2014 Jun 18;7:1071-81. doi: 10.2147/OTT.S62764. eCollection 2014.
Intratumoral injections of recombinant heat shock protein (Hsp)70 were explored for feasibility in patients with brain tumors. Patients aged 4.5-14 years with untreated newly diagnosed tumors (n=12) were enrolled. After tumor resection, five injections of recombinant Hsp70 (total 2.5 mg) were administered into the resection cavity through a catheter. Before administration of Hsp70 and after the last injection, specific immune responses to the autologous tumor lysate were evaluated using the delayed-type hypersensitivity test. Further, peripheral blood was monitored to identify possible changes in lymphocyte subpopulations, cytokine levels, and the cytolytic activity of natural killer cells. The follow-up period in this trial was 12 months. Intratumoral injections of Hsp70 were well tolerated by patients. One patient had a complete clinical response documented by radiologic findings and one patient had a partial response. A positive delayed-type hypersensitivity test was observed in three patients. In peripheral blood, there was a shift from cytokines provided by Th2 cells toward cytokines of a Th1-cell-mediated response. These data corresponded to changes in lymphocyte subpopulations. Immunosuppressive T-regulatory cell levels were also reduced after injection of Hsp70, as well as production of interleukin-10. The cytolytic activity of natural killer cells was unchanged. The present study demonstrates the feasibility of intratumoral delivery of recombinant Hsp70 in patients with cancer. Further randomized clinical trials are recommended to assess the optimum dose of the chaperone, the treatment schedule, and clinical efficacy.
对肿瘤内注射重组热休克蛋白（Hsp）70 治疗脑肿瘤的可行性进行了研究。招募了年龄在 4.5-14 岁、未经治疗的新诊断肿瘤患者（n=12）。肿瘤切除后，通过导管将 2.5 毫克的重组 Hsp70 共五次注入切除腔。在给予 Hsp70 之前和最后一次注射后，使用迟发型超敏反应试验评估对自体肿瘤裂解物的特异性免疫反应。此外，监测外周血以确定淋巴细胞亚群、细胞因子水平和自然杀伤细胞的细胞毒性活性是否发生可能的变化。该试验的随访期为 12 个月。肿瘤内注射 Hsp70 被患者耐受良好。一名患者的影像学检查结果显示完全临床缓解，一名患者部分缓解。三名患者的迟发型超敏反应试验呈阳性。在外周血中，从 Th2 细胞提供的细胞因子向 Th1 细胞介导的反应的细胞因子发生转变。这些数据与淋巴细胞亚群的变化相对应。注射 Hsp70 后，抑制性 T 调节细胞水平以及白细胞介素-10 的产生也降低。自然杀伤细胞的细胞毒性活性保持不变。本研究证明了在癌症患者中进行肿瘤内递重组 Hsp70 的可行性。建议进行更多的随机临床试验，以评估该伴侣的最佳剂量、治疗方案和临床疗效。
