基于海藻酸盐的人工抗原呈递细胞扩增具有记忆特征的功能性 CD8 T 细胞用于过继细胞治疗。
Alginate-based artificial antigen presenting cells expand functional CD8 T cells with memory characteristics for adoptive cell therapy.
机构信息
Department of Biomedical Engineering, School of Medicine, USA; Institute for Cell Engineering, School of Medicine, USA; Department of Pathology, School of Medicine, USA.
Department of Biomedical Engineering, School of Medicine, USA; Translational Tissue Engineering Center, USA; Institute for NanoBioTechnology, USA.
出版信息
Biomaterials. 2025 Feb;313:122773. doi: 10.1016/j.biomaterials.2024.122773. Epub 2024 Aug 24.
The development of artificial Antigen Presenting Cells (aAPCs) has led to improvements in adoptive T cell therapy (ACT), an immunotherapy, for cancer treatment. aAPCs help to streamline the consistent production and expansion of T cells, thus reducing the time and costs associated with ACT. However, several issues still exist with ACT, such as insufficient T cell potency, which diminishes the translational potential for ACT. While aAPCs have been used primarily to increase production efficiency of T cells for ACT, the intrinsic properties of a biomaterial-based aAPC may affect T cell phenotype and function. In CD8 T cells, reactive oxygen species (ROS) and oxidative stress accumulation can activate Forkhead box protein O1 (FOXO1) to transcribe antioxidants which reduce ROS and improve memory formation. Alginate, a biocompatible and antioxidant rich biomaterial, is promising for incorporation into an aAPC formulation to modulate T cell phenotype. To investigate its utility, a novel alginate-based aAPC platform was developed that preferentially expanded CD8 T cells with memory related features. Alginate-based aAPCs allowed for greater control of CD8 T cell qualities, including, significantly improved in vivo persistence and augmented in vivo anti-tumor T cell responses.
人工抗原呈递细胞(aAPC)的发展促进了癌症治疗的过继性 T 细胞疗法(ACT)的免疫疗法的改进。aAPC 有助于简化 T 细胞的一致产生和扩增,从而降低与 ACT 相关的时间和成本。然而,ACT 仍然存在几个问题,例如 T 细胞效力不足,这降低了 ACT 的转化潜力。虽然 aAPC 主要用于提高 ACT 中 T 细胞的生产效率,但基于生物材料的 aAPC 的固有特性可能会影响 T 细胞表型和功能。在 CD8 T 细胞中,活性氧(ROS)和氧化应激积累会激活叉头框蛋白 O1(FOXO1)转录抗氧化剂,从而减少 ROS 并改善记忆形成。藻酸盐是一种生物相容性且富含抗氧化剂的生物材料,有望被纳入 aAPC 配方中以调节 T 细胞表型。为了研究其用途,开发了一种新型的基于藻酸盐的 aAPC 平台,该平台优先扩增具有记忆相关特征的 CD8 T 细胞。基于藻酸盐的 aAPC 允许更好地控制 CD8 T 细胞的质量,包括显著提高体内持久性和增强体内抗肿瘤 T 细胞反应。