肿瘤细胞治疗研究
英文原题：Glioblastoma: Pitfalls and Opportunities of Immunotherapeutic Combinations.
多形性胶质母细胞瘤（GBM）是成人中最常见且最具侵袭性的原发性中枢神经系统肿瘤。
多形性胶质母细胞瘤（GBM）是成人中最常见且最具侵袭性的原发性中枢神经系统肿瘤。其预后极差，因为目前的标准治疗方案——包括大体全切除和替莫唑胺（TMZ）放化疗——虽能延长生存期，但无法提供持久缓解。这在一定程度上归因于GBM异质性、敌意且寒冷的肿瘤微环境（TME），以及GBM克服宿主免疫反应的独特能力。因此，迫切需要开发更有效的治疗方法。本综述从已完成和正在进行的临床研究中提供关键见解，这些研究探讨了针对GBM患者的新型免疫治疗策略，涵盖从在不同GBM治疗场景中使用免疫检查点抑制剂到新型联合疗法。我们特别讨论了基于单抗原肽疫苗的治疗方案如何演变为完全个性化的多价细胞疫苗、CAR-T细胞以及病毒或基因治疗。此外，还综述了最具影响力的临床试验结果以及一系列旨在激活免疫寒冷GBM微环境的创新临床前研究。
Glioblastoma multiforme (GBM) is the most common and aggressive primary central nervous system tumour in adults. It has extremely poor prognosis since the current standard of care, comprising of gross total resection and temozolomide (TMZ) chemoradiotherapy, prolongs survival, but does not provide a durable response. To a certain extent, this is due to GBM's heterogeneous, hostile and cold tumour microenvironment (TME) and the unique ability of GBM to overcome the host's immune responses. Therefore, there is an urgent need to develop more effective therapeutic approaches. This review provides critical insights from completed and ongoing clinical studies investigating novel immunotherapy strategies for GBM patients, ranging from the use of immune checkpoint inhibitors in different settings of GBM treatment to novel combinatorial therapies. In particular, we discuss how treatment regimens based on single antigen peptide vaccines evolved into fully personalised, polyvalent cell-based vaccines, CAR-T cell, and viral or gene therapies. Furthermore, the results of the most influential clinical trials and a selection of innovative preclinical studies aimed at activating the immunologically cold GBM microenvironment are reviewed.
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