磁性纳米粒子能否通过驱动淋巴细胞迁移到肿瘤中来提高采用细胞疗法的效果?

I. Chikileva, Polina Fedorova, I. Shubina, Stanislav Pshenichnikov, Kateryna Levada, Vyacheslav Abramov, M. Kiselevskiy
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摘要

恶性肿瘤的治疗仍然是医疗保健领域的一个巨大难题,因为这些疾病会导致很高的致残率和人口过早死亡。采用细胞疗法治疗恶性肿瘤的主要问题是效应淋巴细胞向肿瘤内迁移的比率较低,以及由于肿瘤微环境的抑制,效应淋巴细胞在肿瘤内的活性较低。此外,应当注意的是,全身静脉注射大量活化淋巴细胞可能会伴随明显的细胞因子释放综合征,从而导致严重的负面影响,包括高热、凝血障碍、免疫细胞对自身组织的攻击,甚至神经毒性。功能性纳米材料,如具有各种表面修饰(PEG、PEI、DMSA、柠檬酸盐等)的磁性纳米粒子,是非常有前景的靶向递送不同抗肿瘤物质的制剂。磁驱动富集肿瘤中的效应抗肿瘤淋巴细胞将大大提高采用淋巴细胞疗法的有效性和安全性。然而,关于这种方法的可行性和效率,不同研究小组获得的数据并不一致。因此,这篇综述主要关注相互矛盾的研究的实验细节,旨在阐明这些争议的可能原因,以及将淋巴细胞有效靶向到肿瘤的最佳做法。
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Can magnetic nanoparticles enhance adoptive cell therapy via driving migration of lymphocytes into tumors?
Therapy of malignant tumors still represents a huge problem for healthcare, since these diseases lead to a high rate of disability and premature death of the population. The main problems of adoptive cell therapy for malignant tumors are a low rate of migration of effector lymphocytes into tumors, as well as their low activity in tumors due to suppressive tumor microenvironment. In addition, it should be noted that systemic intravenous administration of a large number of activated lymphocytes may be accompanied by a pronounced cytokine release syndrome, which leads to significant negative side effects, including high temperature, blood clotting disorders, aggression of immune cells against their own tissues, even neurotoxicity. Functional nanomaterials, such as magnetic nanoparticles with various surface modifications (PEG, PEI, DMSA, citrate, etc.) are highly promising agents for targeted delivery of different anti-tumor substances. Magnet-driven enrichment of effector anti-tumor lymphocytes in tumors would highly increase the effectiveness and enhance safety of adoptive lymphocyte therapy. However, different research groups obtained opposing data about the feasibility and efficiency of such approach. Thus, this review is focused on experimental details of the contradicting studies and aims to elucidate the possible reasons of these controversies and the best practices to efficiently target lymphocytes into tumors.
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