Pharmaceutical Sciences Division, School of Pharmacy, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Carbone Cancer Center, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2024 Sep-Oct;16(5):e2005. doi: 10.1002/wnan.2005.
The adoptive transfer of T cells redirected by chimeric antigen receptors (CARs) has made a dramatic breakthrough in defeating hematological malignancies. However, in solid tumor treatment, CAR-T-cell therapy has attained limited therapeutic benefits due to insufficient infiltration and expansion, rapidly diminishing function following adoptive transfer, and severe life-threatening toxicities. To address these challenges, advancements in nanotechnology have utilized innovative approaches to devise stronger CAR-T cells with reduced toxicity and enhanced anti-tumor activity. Equipping CAR-T cells with multifunctional nanoparticles can abrogate immunosuppressive signaling in the tumor area, augment the functions of CAR-T cells, and mitigate their toxicity against normal tissues. Additionally, nanoparticle-mediated CAR-T-cell programming has the potential to optimize manufacturing and lower the cost for the broader implementation of CAR-T-cell therapy. In this review, we introduce the obstacles to be surmounted in CAR-T-cell therapy, highlight the nanotechnology-based strategies that aim to enrich the therapeutic applications of CAR-T-cell therapy, and envision the prospect of nanoparticle-assisted CAR-T-cell therapy.
嵌合抗原受体 (CAR) 修饰的 T 细胞过继转移在攻克血液恶性肿瘤方面取得了显著突破。然而,在实体瘤治疗中,由于 CAR-T 细胞浸润和扩增不足、过继转移后功能迅速下降以及严重的危及生命的毒性等问题,CAR-T 细胞疗法的治疗效果有限。为了解决这些挑战,纳米技术的进展利用创新方法设计了毒性更低、抗肿瘤活性更强的 CAR-T 细胞。为 CAR-T 细胞配备多功能纳米颗粒可以阻断肿瘤区域的免疫抑制信号,增强 CAR-T 细胞的功能,并减轻其对正常组织的毒性。此外,纳米颗粒介导的 CAR-T 细胞编程有可能优化制造过程并降低成本,从而更广泛地实施 CAR-T 细胞疗法。在这篇综述中,我们介绍了 CAR-T 细胞疗法中需要克服的障碍,强调了基于纳米技术的策略,旨在丰富 CAR-T 细胞疗法的治疗应用,并展望了纳米颗粒辅助 CAR-T 细胞疗法的前景。