A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy.
A systematic review on poly(I:C) and poly-ICLC in glioblastoma: adjuvants coordinating the unlocking of immunotherapy.
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DOI：
10.1186/s13046-021-02017-2
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发表时间：
2021-06-25
期刊：
影响因子：
--
通讯作者：
Smits ELJM
中科院分区：
文献类型：
--
作者：
De Waele J;Verhezen T;van der Heijden S;Berneman ZN;Peeters M;Lardon F;Wouters A;Smits ELJM
免疫疗法目前正在深入研究中，作为胶质母细胞瘤的潜在突破性治疗选择。考虑到胶质母细胞瘤周围的解剖学和免疫学复杂性，淋巴细胞浸润大脑以发展具有记忆的持久免疫将是关键。多肌苷：多胞酸，或聚（I:C），及其衍生物聚- iclc可以作为启动或增强治疗，释放淋巴细胞和其他因子（免疫）治疗军械库对抗胶质母细胞瘤。在这里，我们系统地回顾了poly(I:C)/poly- iclc在胶质母细胞瘤治疗中的作用和疗效，从细胞和小鼠胶质母细胞瘤模型的临床前工作到已报道和正在进行的临床研究。MEDLINE检索到2021年5月15日，以确定临床前（胶质母细胞瘤细胞，小鼠模型）和临床研究，研究胶质母细胞瘤中的poly（I:C）或poly- iclc。根据PRISMA指南进行了系统的审查方法。在ClinicalTrials.gov网站上查询正在进行的临床研究。聚（I:C）对胶质母细胞瘤细胞的直接致瘤作用尚未被描述。相反，聚（I:C）改变了胶质母细胞瘤细胞的免疫学特征，也可以直接杀死它们。在小鼠胶质母细胞瘤模型中，poly（I:C）已显示出作为几种治疗方式的辅助治疗的治疗相关性，包括疫苗接种和免疫检查点阻断。临床上，多聚iclc主要作为树突状细胞或肽疫苗的佐剂，已被证明是安全的，能够激发免疫活性以增强治疗反应。Poly-ICLC可能是一种有价值的工具，可以增强胶质母细胞瘤的免疫治疗方法。最后，我们提出了几种有希望的联合策略，可能会推进胶质母细胞瘤免疫治疗，并讨论了关键的临床前方面，以提高临床翻译。
Immunotherapy is currently under intensive investigation as a potential breakthrough treatment option for glioblastoma. Given the anatomical and immunological complexities surrounding glioblastoma, lymphocytes that infiltrate the brain to develop durable immunity with memory will be key. Polyinosinic:polycytidylic acid, or poly(I:C), and its derivative poly-ICLC could serve as a priming or boosting therapy to unleash lymphocytes and other factors in the (immuno)therapeutic armory against glioblastoma. Here, we present a systematic review on the effects and efficacy of poly(I:C)/poly-ICLC for glioblastoma treatment, ranging from preclinical work on cellular and murine glioblastoma models to reported and ongoing clinical studies. MEDLINE was searched until 15 May 2021 to identify preclinical (glioblastoma cells, murine models) and clinical studies that investigated poly(I:C) or poly-ICLC in glioblastoma. A systematic review approach was conducted according to PRISMA guidelines. ClinicalTrials.gov was queried for ongoing clinical studies. Direct pro-tumorigenic effects of poly(I:C) on glioblastoma cells have not been described. On the contrary, poly(I:C) changes the immunological profile of glioblastoma cells and can also kill them directly. In murine glioblastoma models, poly(I:C) has shown therapeutic relevance as an adjuvant therapy to several treatment modalities, including vaccination and immune checkpoint blockade. Clinically, mostly as an adjuvant to dendritic cell or peptide vaccines, poly-ICLC has been demonstrated to be safe and capable of eliciting immunological activity to boost therapeutic responses. Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.
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