King's College London, Division of Cancer Studies, Guy's Hospital, London, United Kingdom.
King's College London, Division of Cancer Studies, Guy's Hospital, London, United Kingdom; Department of Clinical Immunology and Allergy, King's College Hospital NHS Foundation Trust, London, United Kingdom; Department of Immunology, Eastbourne Hospital, East Sussex, United Kingdom.
Prog Mol Biol Transl Sci. 2019;164:217-292. doi: 10.1016/bs.pmbts.2019.06.015. Epub 2019 Jul 19.
For patients with advanced hematological malignancies the therapeutic landscape has been transformed by the emergence of adoptive cell transfer utilizing autologous chimeric antigen receptor (CAR)-redirected T-cells. However, solid tumors have proved far more resistant to this approach. Here, we summarize the numerous challenges faced by CAR T-cells designed to target solid tumors, highlighting, in particular, issues related to impaired trafficking, expansion, and persistence. In parallel, we draw attention to exciting developments in the burgeoning field of oncolytic virotherapy and posit strategies for the synergistic combination of oncolytic viruses with CAR T-cells to improve outcomes for patients with advanced solid tumors.
对于患有晚期血液恶性肿瘤的患者,嵌合抗原受体 (CAR) 修饰的自体 T 细胞过继转移的出现改变了治疗格局。然而,实体瘤对此方法的反应远较困难。在此,我们总结了旨在靶向实体瘤的 CAR T 细胞所面临的诸多挑战,特别强调了与转导、扩增和持久性受损相关的问题。同时,我们也注意到新兴的溶瘤病毒治疗领域的令人兴奋的进展,并提出了将溶瘤病毒与 CAR T 细胞联合应用的策略,以改善晚期实体瘤患者的治疗效果。