肿瘤细胞治疗研究
英文原题：Pharmacotherapeutic Treatment of Glioblastoma: Where Are We to Date?
胶质母细胞瘤（GBM）的临床管理仍然缺乏能够显著改善该疾病不良预后的治疗方法。
胶质母细胞瘤（GBM）的临床管理仍然缺乏能够显著改善该疾病不良预后的治疗方法。尽管临床对新治疗药物的需求极为迫切，但只有一小部分GBM患者能从参与临床试验中获益。此外，临床研究往往无法得出最终可解释的结论。从过去几年所犯的错误和获得的阴性结果中，我们现在能够为GBM患者规划新一代临床研究，允许同时测试多种抗癌药物。这一点具有至关重要的意义，因为得益于对与该疾病相关的异常分子机制认识的提高，我们现在能够为新诊断和复发性GBM患者提出多种潜在有效的化合物。在已评估的新化合物中，最初对使用免疫检查点抑制剂（ICIs）的试验抱有极大热情，但由于三项随机III期试验出现的阴性结果而令人失望。然而，对该疾病的新生物学见解表明，即使ICIs未能延长这些患者的生存期，免疫治疗在GBM中仍可能是一种令人信服且有效的治疗方法。在这方面，最有前景的方法包括工程化免疫细胞，如嵌合抗原受体（CAR）T、CAR M和CAR NK，单独使用或与其他治疗联合使用。在这篇综述中，我们讨论了与GBM患者全身治疗相关的若干问题。首先，我们评估了临床试验规划中的关键问题以及为克服这些障碍所采用的策略。随后，我们转向针对既往未经治疗（新诊断）GBM患者以及复发和经治患者的 most relevant 干预性研究。最后，我们探讨新型免疫治疗方法，特别强调与在GBM中施用工程化免疫细胞相关的临床前和临床数据。
The clinical management of glioblastoma (GBM) is still bereft of treatments able to significantly improve the poor prognosis of the disease. Despite the extreme clinical need for novel therapeutic drugs, only a small percentage of patients with GBM benefit from inclusion in a clinical trial. Moreover, often clinical studies do not lead to final interpretable conclusions. From the mistakes and negative results obtained in the last years, we are now able to plan a novel generation of clinical studies for patients with GBM, allowing the testing of multiple anticancer agents at the same time. This assumes critical importance, considering that, thanks to improved knowledge of altered molecular mechanisms related to the disease, we are now able to propose several potential effective compounds in patients with both newly diagnosed and recurrent GBM. Among the novel compounds assessed, the initially great enthusiasm toward trials employing immune checkpoint inhibitors (ICIs) was disappointing due to the negative results that emerged in three randomized phase III trials. However, novel biological insights into the disease suggest that immunotherapy can be a convincing and effective treatment in GBM even if ICIs failed to prolong the survival of these patients. In this regard, the most promising approach consists of engineered immune cells such as chimeric antigen receptor (CAR) T, CAR M, and CAR NK alone or in combination with other treatments. In this review, we discuss several issues related to systemic treatments in GBM patients. First, we assess critical issues toward the planning of clinical trials and the strategies employed to overcome these obstacles. We then move on to the most relevant interventional studies carried out on patients with previously untreated (newly diagnosed) GBM and those with recurrent and pretreated disease. Finally, we investigate novel immunotherapeutic approaches with special emphasis on preclinical and clinical data related to the administration of engineered immune cells in GBM.
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