嵌合抗原受体T细胞治疗胰腺导管腺癌的研究进展

Research Progress in Chimeric Antigen Receptor T cell Therapy for Pancreatic Ductal Adenocarcinoma

胰腺导管腺癌(PDAC)是一种恶性程度很高的肿瘤,大多数患者确诊时已为晚期,给予放、化疗等方案治疗疗效欠佳,预后极差。近年来,嵌合抗原受体T细胞(CAR-T细胞)疗法作为肿瘤免疫治疗的新研究热点,已应用于实体肿瘤的治疗,并取得了很好的治疗效果。CAR-T细胞是一种源于基因工程的T细胞,在非主要组织相容性复合体限制的情况下,特异性地结合肿瘤抗原靶点,杀伤肿瘤细胞。在临床前期和临床试验中,CAR-T细胞治疗PDAC已取得了显著进展,但仍存在免疫抑制微环境、间质屏障及脱靶反应等问题。

Pancreatic ductal adenocarcinoma(PDAC)is a highly malignant tumor,and most patients are at advanced stage at the time of diagnosis,when the effect of radiotherapy/chemotherapy is unsatisfactory often with extremely poor prognosis.As a new research hotspot of tumor immunotherapy,chimeric antigen receptor T cell(CAR-T cell)therapy has been applied to solid tumor therapy in recent years,and has achieved good therapeutic effects.CAR-T cell is a genetically engineered T cell that specifically binds tumor antigen targets to kill tumor cells when restricted by non-major histocompatibility complex.In preclinical and clinical trials,CAR-T cell has made significant progress in the treatment of PDAC,but there are still some problems such as immunosuppressive microenvironment,interstitial barrier and off-target response.