CAR T-Cell Therapy for Cancer: Latest Updates and Challenges, with a Focus on B-Lymphoid Malignancies and Selected Solid Tumours

卷:12

Review

关键词: METASTATIC MELANOMA;    OPEN-LABEL;    LONG-TERM;    PHASE-II;    IMMUNOTHERAPY;    IPILIMUMAB;    PEMBROLIZUMAB;    CHEMOTHERAPY;    MULTICENTER;    SURVIVAL;   

DOI  :  10.3390/cells12121586

来源: SCIE

【 摘 要 】

Although exponential progress in treating advanced malignancy has been made in the modern era with immune checkpoint blockade, survival outcomes remain suboptimal. Cellular immunotherapy, such as chimeric antigen receptor T cells, has the potential to improve this. CAR T cells combine the antigen specificity of a monoclonal antibody with the cytotoxic 'power' of T-lymphocytes through expression of a transgene encoding the scFv domain, CD3 activation molecule, and co-stimulatory domains. Although, very rarely, fatal cytokine-release syndrome may occur, CAR T-cell therapy gives patients with refractory CD19-positive B-lymphoid malignancies an important further therapeutic option. However, low-level expression of epithelial tumour-associated-antigens on non-malignant cells makes the application of CAR T-cell technology to common solid cancers challenging, as does the potentially limited ability of CAR T cells to traffic outside the blood/lymphoid microenvironment into metastatic lesions. Despite this, in advanced neuroblastoma refractory to standard therapy, 60% long-term overall survival and an objective response in 63% was achieved with anti GD2-specific CAR T cells.