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免疫预防胰腺癌。

Immunoprevention of Pancreatic Cancer.

机构信息

Center for Cancer Prevention and Drug Development, Department of Medicine, Hem-Onc Section, University of Oklahoma Health Sciences Center, Oklahoma City, OK, United States.

出版信息

Curr Med Chem. 2018;25(22):2576-2584. doi: 10.2174/0929867324666170223153509.

Abstract

BACKGROUND

Pancreatic cancer (PC) is considered an incurable disease due to late diagnosis, rapid spread and negligible response treatment methods, with a 5-year survival rate of only 7%. Hence, there is an urgency in developing novel strategies for PC prevention. This review is focused on discussing the challenges in understanding complex immune functions in tumor microenvironment and host-induced immune responses against tumors, selection of antigens for development of preventive vaccines, lessons from immunoprevention clinical trials and challenges in developing future vaccines.

METHODS

65 original articles were referenced from various sources, based on immunoprevention or criteria pertaining to tumor antigens and immune responses in PC. All these articles were analyzed for the method details and results obtained, and the existing challenges were derived for successful development of clinical immunoprevention strategies.

RESULTS

The analysis of these articles and our experience with preclinical efficacy evaluations of various preventive approaches against PC helped in identifying specific tumor antigens as targets which can overcome tumor cell immune suppression. This review discussed the status of primary, secondary and tertiary preventive vaccines and reasons for failure of therapeutic vaccines. The key parameters for effective vaccination were identified, including stage of the disease for vaccination efficacy, use of appropriate animal models for development of preventive vaccines. Potential of chemopreventive agents as adjuvants in immunoprevention was discussed. This review identified new challenges for development of immunopreventive vaccines.

CONCLUSION

This review analyzed various aspects of vaccine development for immunoprevention of PC and emphasized the challenges for development of immunoprevention strategies.

摘要

背景

胰腺癌(PC)被认为是一种无法治愈的疾病,因为其诊断较晚、扩散迅速且治疗方法收效甚微,其 5 年生存率仅为 7%。因此,开发新的 PC 预防策略迫在眉睫。本综述主要讨论了理解肿瘤微环境中复杂免疫功能和宿主诱导的抗肿瘤免疫反应、选择用于预防性疫苗开发的抗原、免疫预防临床试验的经验教训以及开发未来疫苗的挑战。

方法

参考了来自各种来源的 65 篇原始文章,这些文章均基于免疫预防或与 PC 中的肿瘤抗原和免疫反应相关的标准。分析了所有这些文章的方法细节和结果,并得出了成功开发临床免疫预防策略的现有挑战。

结果

对这些文章的分析以及我们在针对 PC 的各种预防性方法的临床前疗效评估方面的经验,有助于确定特定的肿瘤抗原作为靶点,可以克服肿瘤细胞的免疫抑制。本综述讨论了初级、次级和三级预防性疫苗的现状以及治疗性疫苗失败的原因。确定了有效接种的关键参数,包括接种疗效的疾病阶段、用于开发预防性疫苗的适当动物模型的使用。还讨论了化学预防剂作为免疫预防佐剂的潜力。本综述确定了免疫预防疫苗开发的新挑战。

结论

本综述分析了针对 PC 免疫预防的疫苗开发的各个方面,并强调了开发免疫预防策略的挑战。

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