Kerstetter-Fogle Amber, Shukla Sourabh, Wang Chao, Beiss Veronique, Harris Peggy L R, Sloan Andrew E, Steinmetz Nicole F
Department of Neurological Surgery, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106, USA.
Department of NanoEngineering, University of California San Diego, La Jolla, CA 92093, USA.
Cancers (Basel). 2019 Apr 10;11(4):515. doi: 10.3390/cancers11040515.
Despite aggressive multi-modality treatment with surgery, radiation and chemotherapies, malignant glioma inevitably recurs and has dismal survival rates. Recent progress in immunotherapy has led to a resurgence of interest, and immunotherapies are being investigated for treatment of glioma. However, the unique brain anatomy and a highly immunosuppressive glioma microenvironment pose significant challenges to achieving efficacy. Thus, there is a critical need for assessment of next-generation immunotherapies for glioma. In this study, we have investigated the efficacy of the nanoparticle platform technology based on plant-derived Cowpea mosaic virus like particles (empty CPMV or eCPMV) to instigate a potent immune response against intracranial glioma. CPMV immunotherapy has been shown to efficiently reverse the immunosuppressive tumor microenvironments in pre-clinical murine models of dermal melanoma and metastatic melanoma, metastatic breast cancer, intraperitoneal ovarian cancer and in canine patients with oral melanoma. In the present study, we demonstrate that in situ administration of CPMV immunotherapy in the setting of glioma can effectively recruit unique subset of effector innate and adaptive immune cells to the brain parenchyma while reducing immune suppressive cellular population, leading to regression of intracranial glioma. The in situ CPMV nanoparticle vaccine offers a potent yet safe and localized immunotherapy for intracranial glioma.
尽管采用了手术、放疗和化疗等积极的多模式治疗方法，恶性胶质瘤仍不可避免地复发，生存率极低。免疫疗法的最新进展引发了人们新的兴趣，目前正在研究将免疫疗法用于治疗胶质瘤。然而，独特的脑部解剖结构和高度免疫抑制的胶质瘤微环境对实现疗效构成了重大挑战。因此，迫切需要评估用于治疗胶质瘤的下一代免疫疗法。在本研究中，我们研究了基于植物源豇豆花叶病毒样颗粒（空壳CPMV或eCPMV）的纳米颗粒平台技术激发针对颅内胶质瘤的有效免疫反应的疗效。在皮肤黑色素瘤和转移性黑色素瘤、转移性乳腺癌、腹膜内卵巢癌的临床前小鼠模型以及患有口腔黑色素瘤的犬类患者中，CPMV免疫疗法已被证明能有效逆转免疫抑制性肿瘤微环境。在本研究中，我们证明在胶质瘤背景下原位给予CPMV免疫疗法可有效将独特的效应先天性和适应性免疫细胞亚群募集到脑实质，同时减少免疫抑制细胞群体，从而导致颅内胶质瘤消退。原位CPMV纳米颗粒疫苗为颅内胶质瘤提供了一种有效、安全且局部的免疫疗法。
