Biomaterial-Based Vaccine Induces Regression of Established Intracranial Glioma in Rats
Biomaterial-Based Vaccine Induces Regression of Established Intracranial Glioma in Rats
复制标题
DOI：
10.1007/s11095-010-0361-x
复制
发表时间：
2011-05-01
影响因子：
3.7
通讯作者：
Emerich, Dwaine F.
中科院分区：
文献类型：
--
作者：
Ali, Omar A.;Doherty, Ed;Emerich, Dwaine F.
神经胶质瘤患者的预后很差，开发新的治疗方法至关重要。此前，我们设计了基于聚合物的疫苗，可控制 GM-CSF、CpG 寡核苷酸和肿瘤裂解物呈递，以调节免疫细胞运输和激活，从而促进针对外周肿瘤的有效免疫反应。在这里，我们将该系统的使用扩展到神经胶质瘤。向大鼠颅内注射神经胶质瘤细胞，然后（1周）在肿瘤床中施用聚合物疫苗（含有GM-CSF、CpG和肿瘤裂解物）。对照大鼠用空白基质、含有GM-CSF和CpG的基质或瘤内推注GM-CSF、CpG和肿瘤裂解物进行处理。监测大鼠的存活情况并测试神经功能。存活研究证实了聚合物疫苗的益处，因为 90% 的接种疫苗的大鼠存活超过 100 天。对照大鼠表现出最小的益处。运动测试显示，疫苗接种可以防止因神经胶质瘤生长而导致前肢功能丧失。组织学分析定量证实了肿瘤大小的强劲而快速的减小。当 67% 的幸存者在第二次神经胶质瘤挑战中存活下来时，长期免疫力得到证实。这些研究扩展了之前关于这种肿瘤治疗方法的报告，并证明了神经胶质瘤治疗的进一步发展。
The prognosis for glioma patients is poor, and development of new treatments is critical. Previously, we engineered polymer-based vaccines that control GM-CSF, CpG-oligonucleotide, and tumor-lysate presentation to regulate immune cell trafficking and activation, which promoted potent immune responses against peripheral tumors. Here, we extend the use of this system to glioma.Rats were challenged with an intracranial injection of glioma cells followed (1 week) by administration of the polymeric vaccine (containing GM-CSF, CpG, and tumor-lysate) in the tumor bed. Control rats were treated with blank matrices, matrices with GM-CSF and CpG, or intra-tumoral bolus injections of GM-CSF, CpG, and tumor lysate. Rats were monitored for survival and tested for neurological function.Survival studies confirmed a benefit of the polymeric vaccine as 90% of vaccinated rats survived for > 100 days. Control rats exhibited minimal benefit. Motor tests revealed that vaccination protected against the loss of forelimb use produced by glioma growth. Histological analysis quantitatively confirmed a robust and rapid reduction in tumor size. Long-term immunity was confirmed when 67% of survivors also survived a second glioma challenge.These studies extend previous reports regarding this approach to tumor therapy and justify further development for glioma treatment.