Chouari Tarak, La Costa Francesca Soraya, Merali Nabeel, Jessel Maria-Danae, Sivakumar Shivan, Annels Nicola, Frampton Adam E
Hepato-Pancreato-Biliary Department, Royal Surrey NHS Foundation Trust, Guildford GU2 7XX, UK.
Section of Oncology, Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7WG, UK.
Cancers (Basel). 2023 Aug 25;15(17):4265. doi: 10.3390/cancers15174265.
Pancreatic ductal adenocarcinoma (PDAC) accounts for up to 95% of all pancreatic cancer cases and is the seventh-leading cause of cancer death. Poor prognosis is a result of late presentation, a lack of screening tests and the fact some patients develop resistance to chemotherapy and radiotherapy. Novel therapies like immunotherapeutics have been of recent interest in pancreatic cancer. However, this field remains in its infancy with much to unravel. Immunotherapy and other targeted therapies have yet to yield significant progress in treating PDAC, primarily due to our limited understanding of the disease immune mechanisms and its intricate interactions with the tumour microenvironment (TME). In this review we provide an overview of current novel immunotherapies which have been studied in the field of pancreatic cancer. We discuss their mechanisms, evidence available in pancreatic cancer as well as the limitations of such therapies. We showcase the potential role of combining novel therapies in PDAC, postulate their potential clinical implications and the hurdles associated with their use in PDAC. Therapies discussed with include programmed death checkpoint inhibitors, Cytotoxic T-lymphocyte-associated protein 4, Chimeric Antigen Receptor-T cell therapy, oncolytic viral therapy and vaccine therapies including KRAS vaccines, Telomerase vaccines, Gastrin Vaccines, Survivin-targeting vaccines, Heat-shock protein (HSP) peptide complex-based vaccines, MUC-1 targeting vaccines, Listeria based vaccines and Dendritic cell-based vaccines.
胰腺导管腺癌(PDAC)占所有胰腺癌病例的95%,是癌症死亡的第七大原因。预后不良是由于就诊晚、缺乏筛查测试以及一些患者对化疗和放疗产生耐药性。免疫疗法等新型疗法最近在胰腺癌治疗中受到关注。然而,该领域仍处于起步阶段,有许多有待揭示的问题。免疫疗法和其他靶向疗法在治疗PDAC方面尚未取得显著进展,主要是因为我们对该疾病的免疫机制及其与肿瘤微环境(TME)的复杂相互作用了解有限。在本综述中,我们概述了目前在胰腺癌领域研究的新型免疫疗法。我们讨论了它们的机制、胰腺癌中的现有证据以及此类疗法的局限性。我们展示了联合新型疗法在PDAC中的潜在作用,推测了它们的潜在临床意义以及在PDAC中使用所面临的障碍。所讨论的疗法包括程序性死亡检查点抑制剂、细胞毒性T淋巴细胞相关蛋白4、嵌合抗原受体T细胞疗法、溶瘤病毒疗法以及疫苗疗法,包括KRAS疫苗、端粒酶疫苗、胃泌素疫苗、靶向生存素的疫苗、基于热休克蛋白(HSP)肽复合物的疫苗、靶向MUC-1的疫苗、基于李斯特菌的疫苗和基于树突状细胞的疫苗。