决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Tumor Microenvironment in Neuroblastoma and Immunotherapeutic Approaches: Towards More Effective Treatment.
Tumor Microenvironment in Neuroblastoma and Immunotherapeutic Approaches: Towards More Effective Treatment.
背景/目的:高危神经母细胞瘤(HR-NB)是儿童癌症相关死亡的主要原因之一。
背景/目的:高危神经母细胞瘤(HR-NB)是儿童癌症相关死亡的主要原因之一。本综述旨在探讨神经母细胞瘤(NB)的各种生化和遗传特征,以评估其在细胞疗法中的潜在应用。方法:通过MEDLINE、PubMed、Scopus和ScienceDirect数据库,使用“神经母细胞瘤”、“肿瘤微环境(TME)”、“免疫细胞”、“非免疫细胞”、“造血干细胞移植(HSCT)”、“自体干细胞移植(ASCT)”、“NK 细胞”、“CAR-T 细胞”、“CAR-NKT”、“TIL(肿瘤浸润淋巴细胞)”、“生物信息学”和“神经抗原”等关键词组合,对过去十年发表的相关文献进行了全面检索。选取了与儿童NB相关的综述、系统评价和临床试验,最终纳入106篇相关文章。结果:近期研究表明,TME在决定NB的恶性程度、免疫逃逸和耐药性方面至关重要。先天免疫细胞或非免疫细胞在塑造NB TME中发挥重要作用。清除或重编程TME因素可提高免疫治疗的有效性。多项临床试验已研究并证明了在HR-NB过继性治疗中使用ASCT、NK细胞、CAR-T和CAR-NKT细胞的可行性。然而,由于缺乏大规模随机试验,对细胞技术在HR-NB治疗中有效性的明确评估仍较为复杂。结论:已报道的小规模和非随机研究结果存在争议,无法确凿证明包括ASCT、NK、CAR-T和CAR-NKT细胞在内的细胞技术具有显著潜力。使用相同治疗方案的进一步随机临床试验,将有助于确定其在高危神经母细胞瘤(HR-NB)多模式治疗中的作用。
Background/Objectives : High-risk neuroblastoma (HR-NB) is a major cause of cancer-related death among children. The review aims to discuss various biochemical and genetic traits of neuroblastoma (NB) used for the potential of cell-based therapies. Methods : A comprehensive search was performed through MEDLINE, PubMed, Scopus, and ScienceDirect using various combinations of "neuroblastoma", "tumor microenvironment (TME)", "immune cells", "non-immune cells", "hematopoietic stem cell transplantation (HSCT)", "autologous stem cell transplantation (ASCT)", "natural killer cells (NK)", "chimeric antigen receptor T cells (CAR-T)", "CAR-NKT", "tumor infiltrating lymphocytes (TIL)", "bioinformatics", and "neuro-antigens" in the published papers over the last decade. Reviews, systematic reviews, and clinical trials related to children's NB were selected. The final set included 106 articles of interest. Results : Recent studies have shown that TME is crucial in determining the malignancy, immune evasion, and drug resistance of NB. Innate immune or non-immune cells play important roles in shaping the NB TME. Depleting or reprogramming TME factors can improve the effectiveness of immunotherapy. A number of clinical trials have studied and showed feasibility of using ASCT, NK cells, CAR-T, and CAR-NKT cells in the adoptive therapy for HR-NB. However, an unambiguous evaluation of the effectiveness of cell-based technologies in the HR-NB therapy is still complicated due to the lack of large randomized trials. Conclusions : The reported small and non-randomized studies that demonstrated controversial results cannot prove, undoubtedly, the promising potential of the cell-based technologies including ASCT, NKs, CAR-T, and CAR-NKT cells. Further randomized clinical trials, using the same treatment, will help determine the role in the multimodal treatment for HR-NB.
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