Testa Ugo, Castelli Germana, Pelosi Elvira
Department of Oncology, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, Italy.
Cancers (Basel). 2024 Aug 22;16(16):2913. doi: 10.3390/cancers16162913.
Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy has been particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity, the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising antitumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies.
嵌合抗原受体T细胞(CAR-T)在血液系统恶性肿瘤中显示出显著疗效,但在实体瘤中的反应有限。在实体瘤中,CAR-T细胞疗法在脑肿瘤中得到了特别的探索。由于多种因素阻碍了其活性,CAR-T细胞在各种类型的脑肿瘤中显示出有限的临床疗效,这些因素包括肿瘤抗原异质性、CAR-T细胞进入脑肿瘤细胞的机会有限、CAR-T细胞的迁移和体内持久性受限以及高度免疫抑制性肿瘤微环境的存在。尽管有这些考虑因素,但最近的一些研究表明,GD2-CAR-T细胞对弥漫性中线胶质瘤和神经母细胞瘤以及CARv3-TEAM-E细胞对胶质母细胞瘤具有有前景的抗肿瘤活性。然而,需要采取策略来提高CAR-T细胞在脑肿瘤中的效果,包括具有多种抗原靶向的先进CAR-T细胞设计以及联合疗法的应用。