Application prospects of tumor vaccines for pancreatic cancer: From TAAs to TSAs and combination strategies

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology Pub Date : 2025-08-20 DOI:10.1016/j.seminoncol.2025.152399

Zerui Lu , Wenxin Zhu , Xinjian Liu

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引用次数: 0

Abstract

Pancreatic cancer, a highly aggressive malignancy of the digestive system, exhibits therapeutic resistance due to its immunosuppressive tumor microenvironment (TME) and early metastatic potential. Cancer vaccines targeting tumor-associated antigens (TAAs) or tumor-specific antigens (TSAs) have emerged as promising immunotherapeutic strategies. TAA-based vaccines demonstrate T cell activation and tumor suppression in preclinical models, yet face limitations from antigen heterogeneity and immunosuppressive TME. TSA-directed vaccines, exemplified by personalized mRNA vaccines incorporating whole-exome sequencing-selected neoantigens, achieved long-term recurrence-free survival in 50% of vaccinated patients during phase I/II trials, with phase III data supporting synergistic efficacy when combined with chemotherapy and programmed death receptor 1 (PD-1) inhibitors. KRAS-targeted vaccines address common mutations (e.g., G12D, G12V) to broaden applicability. This review presents an updated summary of current tumor vaccine types, mechanisms, and clinical implications, while analyzing how combination therapies remodel TME infiltration and reverse T cell exhaustion to significantly improve survival outcomes. The discussion also addresses existing challenges and proposes future directions in pancreatic cancer vaccine development.

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胰腺癌肿瘤疫苗的应用前景：从TAAs到TSAs及联合策略

胰腺癌是一种高度侵袭性的消化系统恶性肿瘤，由于其免疫抑制肿瘤微环境（TME）和早期转移潜力而表现出治疗耐药性。针对肿瘤相关抗原（TAAs）或肿瘤特异性抗原（TSAs）的癌症疫苗已成为有前途的免疫治疗策略。基于taa的疫苗在临床前模型中显示出T细胞活化和肿瘤抑制，但面临抗原异质性和免疫抑制TME的限制。tsa导向疫苗，以结合全外显子组测序选择的新抗原的个性化mRNA疫苗为例，在I/II期试验中，50%接种疫苗的患者实现了长期无复发生存，III期数据支持与化疗和程序性死亡受体1 （PD-1）抑制剂联合使用时的协同效果。针对kras的疫苗针对常见突变（例如G12D、G12V），以扩大适用性。本文综述了当前肿瘤疫苗类型、机制和临床意义的最新总结，同时分析了联合治疗如何重塑TME浸润和逆转T细胞衰竭以显着改善生存结果。讨论还涉及现有的挑战，并提出胰腺癌疫苗开发的未来方向。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Seminars in oncology 医学-肿瘤学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

104 days

期刊介绍： Seminars in Oncology brings you current, authoritative, and practical reviews of developments in the etiology, diagnosis and management of cancer. Each issue examines topics of clinical importance, with an emphasis on providing both the basic knowledge needed to better understand a topic as well as evidence-based opinions from leaders in the field. Seminars in Oncology also seeks to be a venue for sharing a diversity of opinions including those that might be considered "outside the box". We welcome a healthy and respectful exchange of opinions and urge you to approach us with your insights as well as suggestions of topics that you deem worthy of coverage. By helping the reader understand the basic biology and the therapy of cancer as they learn the nuances from experts, all in a journal that encourages the exchange of ideas we aim to help move the treatment of cancer forward.