摘要
Chimeric antigen receptor T (CAR-T) cells have achieved breakthrough efficacies against hematological malignancies, but their unsatisfactory efficacies in solid tumors limit their applications. The prohibitively high prices further restrict their access to broader populations. Novel strategies are urgently needed to address these challenges, and engineering biomaterials can be one promising approach. The established process for manufacturing CAR-T cells involves multiple steps, and biomaterials can help simplify or improve several of them. In this review, we cover recent progress in engineering biomaterials for producing or stimulating CAR-T cells. We focus on the engineering of non-viral gene delivery nanoparticles for transducing CAR into T cells ex vivo/in vitro or in vivo. We also dive into the engineering of nano-/microparticles or implantable scaffolds for local delivery or stimulation of CAR-T cells. These biomaterial-based strategies can potentially change the way CAR-T cells are manufactured, significantly reducing their cost. Modulating the tumor microenvironment with the biomaterials can also considerably enhance the efficacy of CAR-T cells in solid tumors. We pay special attention to progress made in the past five years, and perspectives on future challenges and opportunities are also discussed.
摘要译文
嵌合抗原受体T（CAR-T）细胞已经对血液系统恶性肿瘤达到了突破性的效力，但是它们在实体瘤中的效力不令人满意，限制了其应用。高昂的价格进一步限制了他们进入更广泛的人口的机会。迫切需要采取新颖的策略来应对这些挑战，工程生物材料可能是一种有前途的方法。制造CAR-T细胞的既定过程涉及多个步骤，生物材料可以帮助简化或改善其中的几个步骤。在这篇综述中，我们介绍了生产或刺激CAR-T细胞的工程生物材料的最新进展。我们专注于非病毒基因递送纳米颗粒的工程，以将汽车转导到T细胞中，体外或体内。我们还深入研究纳米/微粒或可植入的支架的工程，用于局部输送或刺激CAR-T细胞。这些基于生物材料的策略可能会改变CAR-T细胞的制造方式，从而大大降低其成本。与生物材料调节肿瘤微环境也可以大大提高CAR-T细胞在实体瘤中的疗效。我们特别注意过去五年中取得的进步，还讨论了对未来挑战和机遇的观点。
Wujin Sun [a] [c] [d]. Biomaterials for chimeric antigen receptor T cell engineering[J]. Acta Biomaterialia, 2023,166: 1-13