Center for Cell-Encapsulation Research, Department of Chemistry, KAIST, Daejeon, 34141, Korea.
Department of Chemistry and Chemistry Institute of Functional Materials, Pusan National University, Busan, 46241, Korea.
Angew Chem Int Ed Engl. 2017 Aug 28;56(36):10702-10706. doi: 10.1002/anie.201703886. Epub 2017 Jun 19.
Lymphocytes, such as T cells and natural killer (NK) cells, have therapeutic promise in adoptive cell transfer (ACT) therapy, where the cells are activated and expanded in vitro and then infused into a patient. However, the in vitro preservation of labile lymphocytes during transfer, manipulation, and storage has been one of the bottlenecks in the development and commercialization of therapeutic lymphocytes. Herein, we suggest a cell-in-shell (or artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy. A durable titanium oxide (TiO ) shell is formed on individual Jurkat T cells, and the CD3 and other antigens on cell surfaces remain accessible to the antibodies. Interleukin-2 (IL-2) secretion is also not hampered by the shell formation. This work suggests a chemical toolbox for effectively preserving lymphocytes in vitro and developing the lymphocyte-based cancer immunotherapy.
淋巴细胞,如 T 细胞和自然杀伤 (NK) 细胞,在过继细胞转移 (ACT) 治疗中有治疗潜力,其中细胞在体外被激活和扩增,然后输注到患者体内。然而,在转移、操作和储存过程中保持不稳定淋巴细胞的体外保存一直是治疗性淋巴细胞的开发和商业化的瓶颈之一。在这里,我们建议采用细胞壳(或人工孢子)策略来提高细胞在实际环境中的存活率,同时保持治疗功效的生物活性。单个 Jurkat T 细胞上形成了耐用的氧化钛 (TiO ) 壳,细胞表面上的 CD3 和其他抗原仍然可以与抗体结合。壳的形成也不会阻碍白细胞介素-2 (IL-2) 的分泌。这项工作为有效地在体外保存淋巴细胞和开发基于淋巴细胞的癌症免疫疗法提供了一个化学工具箱。