Department of Pancreatic Surgery, Shanghai Cancer Centre, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Med. 2019 Sep;8(11):5223-5231. doi: 10.1002/cam4.2430. Epub 2019 Jul 3.
Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant cancer with limited treatment options. Chimeric antigen receptor T cells (CAR-T) are genetically engineered T cells that can specifically kill tumor cells without major histocompatibility complex restriction. Encouraging progress in CAR-T therapy for PDAC has been made in preclinical and early phase clinical trials. Challenges in CAR-T therapy for solid tumors still exist, including immunosuppressive microenvironment, interstitial barrier, poor chemotaxis, and the "on-target, off-tumor" effect. Applying neoantigens of PDAC as targets for CAR-T therapy, recognizing the CAR-T subgroup with better antitumor effect, and designing a CAR-T system targeting stroma of PDAC may contribute to develop a powerful CAR-T therapy for PDAC in the future.
胰腺导管腺癌（PDAC）是一种高度恶性的癌症，治疗选择有限。嵌合抗原受体 T 细胞（CAR-T）是经过基因工程改造的 T 细胞，可以特异性地杀死肿瘤细胞，而不受主要组织相容性复合体的限制。在 PDAC 的 CAR-T 治疗的临床前和早期临床试验中取得了令人鼓舞的进展。CAR-T 治疗实体瘤仍然存在挑战，包括免疫抑制微环境、间质屏障、趋化性差和“靶内脱靶”效应。将 PDAC 的新抗原作为 CAR-T 治疗的靶点，识别具有更好抗肿瘤效果的 CAR-T 亚群，并设计针对 PDAC 基质的 CAR-T 系统，可能有助于未来开发强大的 PDAC CAR-T 治疗方法。
