School of Materials Science and Engineering, South China University of Technology, Guangzhou 510640, China.
National Key Laboratory of Immunity & Inflammation, Institute of Immunology, Naval Medical University, Shanghai 200433, China; Department of Clinical Laboratory, Third Affiliated Hospital of Naval Medical University, Shanghai 200438, China.
Colloids Surf B Biointerfaces. 2024 Jul;239:113977. doi: 10.1016/j.colsurfb.2024.113977. Epub 2024 May 16.
Adoptive T cell therapy has undergone remarkable advancements in recent decades; nevertheless, the rapid and effective ex vivo expansion of tumor-reactive T cells remains a formidable challenge, limiting their clinical application. Artificial antigen-presenting substrates represent a promising avenue for enhancing the efficiency of adoptive immunotherapy and fostering T cell expansion. These substrates offer significant potential by providing flexibility and modularity in the design of tailored stimulatory environments. Polydimethylsiloxane (PDMS) silicone elastomer stands as a widely utilized biomaterial for exploring the varying sensitivity of T cell activation to substrate properties. This paper explores the optimization of PDMS surface modification and formulation to create customized stimulatory surfaces with the goal of enhancing T cell expansion. By employing soft PDMS elastomer functionalized through silanization and activating agent, coupled with site-directed protein immobilization techniques, a novel T cell stimulatory platform is introduced, facilitating T cell activation and proliferation. Notably, our findings underscore that softer modified elastomers (Young' modulus E∼300 kPa) exhibit superior efficacy in stimulating and activating mouse CD4 T cells compared to their stiffer counterparts (E∼3 MPa). Furthermore, softened modified PDMS substrates demonstrate enhanced capabilities in T cell expansion and Th1 differentiation, offering promising insights for the advancement of T cell-based immunotherapy.
近年来，过继性 T 细胞疗法取得了显著进展；然而，快速有效地体外扩增肿瘤反应性 T 细胞仍然是一个巨大的挑战，限制了它们的临床应用。人工抗原呈递底物为增强过继免疫疗法的效率和促进 T 细胞扩增提供了一条有前途的途径。这些底物通过在设计定制的刺激环境方面提供灵活性和模块化，具有显著的潜力。聚二甲基硅氧烷（PDMS）硅橡胶作为一种广泛应用的生物材料，用于探索 T 细胞对底物特性的激活敏感性的变化。本文探讨了 PDMS 表面修饰和配方的优化，以创建定制的刺激表面，从而增强 T 细胞的扩增。通过使用硅烷化和活化剂功能化的软 PDMS 弹性体，并结合定点蛋白固定技术，引入了一种新型的 T 细胞刺激平台，促进了 T 细胞的激活和增殖。值得注意的是，我们的研究结果表明，与较硬的弹性体（E∼3 MPa）相比，较软的修饰弹性体（E∼300 kPa）在刺激和激活小鼠 CD4 T 细胞方面具有更高的效果。此外，软化修饰的 PDMS 基质在 T 细胞扩增和 Th1 分化方面表现出增强的能力，为基于 T 细胞的免疫疗法的发展提供了有希望的见解。
