Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with high recurrence rates even after curative resection and adjuvant chemotherapy. Although immunotherapeutic approaches, such as immune checkpoint blockade (ICB), have revolutionized the treatment of some solid tumor malignancies, this has not been the case for PDAC. Several characteristics of PDAC, including its distinctive desmoplastic tumor microenvironment (TME), intratumor heterogeneity, and poor antigenicity and immune cell infiltration, contribute to its dismal immunotherapeutic landscape. Cancer vaccines offer one approach to overcoming these barriers, particularly in the resectable or borderline resectable settings, where tumor burden is low and immunosuppression is less pronounced. Various vaccination platforms have been tested in the clinical setting, from off-the-shelf peptide-based vaccines (e.g., AMPLFIFY-201 study, where over 80% of participants exhibited T-cell and biomarker responses) to personalized neoantigen mRNA vaccine approaches (e.g., autogene cevumeran, with significant responders experiencing longer median recurrence-free survival (RFS)). The key considerations for enhancing the efficacy of vaccination include combinations with chemotherapy, radiotherapy, and/or ICBs, as well as selecting appropriate immunomodulators or adjuvants. Recent results suggest that with continued mechanistic advancement and novel therapeutic development, cancer vaccines may finally be poised for clinical success in PDAC.
胰腺导管腺癌（PDAC）是一种侵袭性恶性肿瘤，即使经过根治性切除和辅助化疗后仍具有高复发率。尽管免疫治疗方法，如免疫检查点阻断（ICB），已彻底改变了一些实体恶性肿瘤的治疗，但PDAC的情况并非如此。PDAC的若干特征，包括其独特的促纤维增生性肿瘤微环境（TME）、肿瘤内异质性、以及较差的抗原性和免疫细胞浸润，共同导致了其免疫治疗前景的黯淡。癌症疫苗为克服这些障碍提供了一种途径，特别是在可切除或临界可切除的情况下，此时肿瘤负荷较低且免疫抑制程度较轻。多种疫苗平台已在临床环境中进行了测试，从现成的基于肽的疫苗（例如AMPLFIFY-201研究，其中超过80%的参与者表现出T细胞和生物标志物反应）到个性化的新抗原mRNA疫苗方法（例如autogene cevumeran，显著应答者经历了更长的中位无复发生存期（RFS））。提高疫苗接种疗效的关键考虑因素包括与化疗、放疗和/或ICB的联合应用，以及选择合适的免疫调节剂或佐剂。最近的研究结果表明，随着机制的不断进步和新疗法的开发，癌症疫苗可能最终在PDAC中取得临床成功。
Cancer Vaccination and Immune-Based Approaches in Pancreatic Cancer
肿瘤(癌症)患者之家