肿瘤细胞治疗研究
英文原题：Immune response recalibration using immune therapy and biomimetic nano-therapy against high-grade gliomas and brain metastases.
Immune response recalibration using immune therapy and biomimetic nano-therapy against high-grade gliomas and brain metastases.
尽管采用了手术切除、化疗和放疗等积极的标准治疗，高级别胶质瘤（HGGs）和脑转移（BM）的治疗在二十多年里仍具挑战性。
尽管采用手术切除、化疗和放疗等强化标准治疗，高级别胶质瘤（HGG）和脑转移瘤（BM）的治疗二十多年来仍具挑战。然而，相关技术进步和免疫治疗策略已改变HGG及BM的治疗格局。免疫检查点抑制剂、靶向CAR-T、溶瘤病毒疗法、双特异性抗体治疗和疫苗等免疫疗法正成为有前景的新方向，有望进一步改善患者生存。选择性穿越血脑屏障（BBB）、免疫抑制性肿瘤微环境（TME）、代谢改变及肿瘤异质性，则限制了免疫治疗对HGG和BM的疗效。为应对这些问题，基于纳米生物技术的仿生递送系统近年来受到广泛关注。相关技术包括“特洛伊木马”靶向，以及用免疫细胞、红细胞、血小板、胶质瘤细胞裂解物等生物分子或细胞包覆、伪装纳米颗粒表面，或整合这些策略形成具有同型识别能力的杂合膜。与传统纳米颗粒相比，这些仿生纳米疗法可提高靶向特异性、循环稳定性和活性载荷能力，改善BBB通透性（利用中性粒细胞固有的炎症趋化性），降低免疫原性，产生基于代谢的有效联合效应，并通过诱导免疫记忆预防肿瘤复发，有望改善HGG和BM免疫治疗结局。本综述重点讨论神经免疫治疗及多功能仿生纳米递送策略在精准靶向难治性、高致死性HGG和BM中的应用，并探讨阻碍其临床转化的挑战及脑肿瘤尚未满足的医疗需求。
Although with aggressive standards of care like surgical resection, chemotherapy, and radiation, high-grade gliomas (HGGs) and brain metastases (BM) treatment has remained challenging for more than two decades. However, technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM. Immunotherapies like immune checkpoint inhibitors, CAR-T targeting, oncolytic virus-based therapy, bispecific antibody treatment, and vaccination approaches, etc., are emerging as promising avenues offering new hope in refining patient's survival benefits. However, selective trafficking across the blood-brain barrier (BBB) , immunosuppressive tumor microenvironment (TME), metabolic alteration, and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM. Furthermore, to address this concern, the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years. With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes, erythrocytes, platelets, glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition. These biomimetic nanotherapy offers advantages over conventional nanoparticles, focusing on greater target specificity, increased circulation stability, higher active loading capacity, BBB permeability (inherent inflammatory chemotaxis of neutrophils), decreased immunogenicity, efficient metabolism-based combinatorial effects, and prevention of tumor recurrence by induction of immunological memory, etc. provide new age of improved immunotherapies outcomes against HGGs and BM. In this review, we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat and most lethal HGGs and BM. Moreover, the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.
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