Genetically modified T cells in cancer therapy: opportunities and challenges
基因修饰的T细胞在癌症治疗的机遇与挑战
ABSTRACT
Tumours use many strategies to evade the host immune response,including down regulation or weak immunogenicity of target antigens and creation of an immune-suppressive tumour environment. T cells play a key role in cell-mediated immunity and, recently, strategies to genetically modify T cells either through altering the specificity of the T cell receptor (TCR) or through introducing antibody-like recognition in chimeric antigen receptors (CARs) have made substantial advances. The potential of these approaches has been demonstrated
in particular by the successful use of genetically modified T cells to treat B cell hematologic malignancies in clinical trials. This clinical success is reflected in the growing number of strategic partnerships in this area that have attracted a high level of investment and involve large pharmaceutical organisations. Although our understanding of the factors that influence the safety and efficacy of these therapies has increased, challenges for bringing genetically modified T-cellimmunotherapy to many patients with different tumour types remain.These challenges range from the selection of antigen targets and dealing with regulatory and safety issues to successfully navigating the routes to commercial development. However, the encouraging clinical data, the progress in the scientific understanding of tumour immunology and the improvements in the manufacture of cell products are all advancing the clinical translation of these important cellular immunotherapies.
爱康得生物编译
肿瘤通过下调或减弱靶抗原的免疫原性以及通过抑制免疫细胞活性在内的多种方式逃避宿主的免疫识别。最近通过构建嵌合抗原受体T细胞和TCR受体T细胞的策略已在细胞介导的免疫治疗中发挥关键作用并取得了实质性进步。这些方法的潜力已被证明，特别是在临床试验中CAR-T治疗恶性血液病获得巨大成功。这些临床的成功更是吸引了大量的投资并和大型制药企业在形成战略合作伙伴关系。虽然我们对该疗法的安全性因素和疗效的理解正在不断的深入，但是挑战仍然存在于对不同肿瘤类型的治疗上，包括对抗原指标的选择，处理，监管和安全问题。不过，令人鼓舞的临床资料表明，随着对肿瘤免疫学的科学认识的深入和细胞产品的生产技术的改进都促进了这些重要的细胞免疫治疗的临床转化。
