Tian Yishen, Chen Wei, Du Guangshi, Gao Jie, Zhao Youbo, Wang Zhuli, Su Min, Hu Rong, Han Feng
Translational Medicine Research Center, Guizhou Medical University, Guiyang 550025, People's Republic of China.
Key Laboratory for Research on Autoimmune Diseases of Higher Education schools in Guizhou Province, Guiyang 550025, People's Republic of China.
Biofabrication. 2024 Mar 15;16(2). doi: 10.1088/1758-5090/ad2fd4.
Adoptive T-cell transfer for cancer therapy is limited by the inefficiency ofT-cell expansion and the ability ofT-cells to infiltrate tumors. The construction of multifunctional artificial antigen-presenting cells is a promising but challenging approach to achieve this goal. In this study, a multifunctional artificial antigen-presenting gel droplet (AAPGD) was designed. Its surface provides regulated T-cell receptor (TCR) stimulation and co-stimulation signals and is capable of slow release of mitogenic cytokines and collagen mimetic peptide. The highly uniform AAPGD are generated by a facile method based on standard droplet microfluidic devices. The results of the study indicate that, T-cell proliferatedutilizing AAPGD have a fast rate and high activity. AAPGD increased the proportion ofproliferating T cells low differentiation and specificity. The starting number of AAPGDs and the quality ratio of TCR-stimulated and co-stimulated signals on the surface have a large impact on the rapid proliferation of low-differentiated T cells. During reinfusion therapy, AAPGD also enhanced T-cell infiltration into the tumor site. In experiments using AAPGD for adoptive T cell therapy in melanoma mice, tumor growth was inhibited, eliciting a potent cytotoxic T-lymphocyte immune response and improving mouse survival. In conclusion, AAPGD promotes rapid low-differentiation proliferation of T cellsand enhances T cell infiltration of tumors. It simplifies the preparation steps of adoptive cell therapy, improves the therapeutic effect, and provides a new pathway for overdosing T cells to treat solid tumors.
用于癌症治疗的过继性T细胞转移受到T细胞扩增效率低下以及T细胞浸润肿瘤能力的限制。构建多功能人工抗原呈递细胞是实现这一目标的一种有前景但具有挑战性的方法。在本研究中,设计了一种多功能人工抗原呈递凝胶微滴(AAPGD)。其表面提供可控的T细胞受体(TCR)刺激和共刺激信号,并且能够缓慢释放促有丝分裂细胞因子和胶原模拟肽。高度均匀的AAPGD通过基于标准微滴微流控装置的简便方法生成。研究结果表明,利用AAPGD增殖的T细胞具有快速的增殖速率和高活性。AAPGD增加了增殖T细胞的比例,降低了分化程度并提高了特异性。AAPGD的起始数量以及表面TCR刺激信号与共刺激信号的质量比,对低分化T细胞的快速增殖有很大影响。在再输注治疗期间,AAPGD还增强了T细胞向肿瘤部位的浸润。在使用AAPGD对黑色素瘤小鼠进行过继性T细胞治疗的实验中,肿瘤生长受到抑制,引发了强烈的细胞毒性T淋巴细胞免疫反应并提高了小鼠存活率。总之,AAPGD促进T细胞快速低分化增殖并增强T细胞对肿瘤的浸润。它简化了过继性细胞治疗的制备步骤,提高了治疗效果,并为大量使用T细胞治疗实体瘤提供了一条新途径。
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