基因修饰的T细胞在癌症治疗的机遇与挑战

爱康得

Genetically modified T cellsin 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 immuneresponse,including down regulation or weak immunogenicity of target antigensand creation of an immune-suppressive tumour environment. T cells play a keyrole in cell-mediated immunity and, recently, strategies to genetically modifyT cells either through altering the specificity of the T cell receptor (TCR) orthrough introducing antibody-like recognition in chimeric antigen receptors(CARs) have made substantial advances. The potential of these approaches hasbeen demonstrated

in particular by the successful use of genetically modifiedT cells to treat B cell hematologic malignancies in clinical trials. Thisclinical success is reflected in the growing number of strategic partnershipsin this area that have attracted a high level of investment and involve largepharmaceutical organisations. Although our understanding of the factors thatinfluence the safety and efficacy of these therapies has increased, challengesfor bringing genetically modified T-cellimmunotherapy to many patients withdifferent tumour types remain.These challenges range from the selection ofantigen targets and dealing with regulatory and safety issues to successfullynavigating the routes to commercial development. However, the encouragingclinical data, the progress in the scientific understanding of tumour immunologyand the improvements in the manufacture of cell products are all advancing theclinical 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。