摘要
背景:胰腺癌(PC)被认为是一种不治之症,由于诊断晚,传播快,治疗方法可忽略不计,5年生存率仅为7%。因此,迫切需要制定预防PC的新战略。本文就肿瘤微环境中复杂免疫功能和宿主诱导的肿瘤免疫应答的认识、预防疫苗研制抗原的选择、免疫预防临床试验的经验教训以及未来疫苗开发面临的挑战等问题进行了综述。方法:根据免疫预防或PC中有关肿瘤抗原和免疫应答的标准,参考来自不同来源的65篇原始文献。结果:对这些文献进行了分析,并对各种预防方法进行了临床前疗效评价,有助于识别特定的肿瘤抗原作为克服肿瘤细胞免疫抑制的靶点。本文综述了初级、二级和三级预防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,包括疫苗接种效果的疾病阶段、使用适当的动物模型开发预防疫苗。探讨了化学预防剂在免疫预防中的应用潜力。结论:分析了PC免疫预防疫苗开发的各个方面,强调了免疫预防策略的发展面临的挑战。
关键词: 胰腺癌,免疫预防,疫苗,早期检测,生物标志物,佐剂。
Current Medicinal Chemistry
Title:Immunoprevention of Pancreatic Cancer
Volume: 25 Issue: 22
关键词: 胰腺癌,免疫预防,疫苗,早期检测,生物标志物,佐剂。
摘要: 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.
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Cite this article as:
Immunoprevention of Pancreatic Cancer, Current Medicinal Chemistry 2018; 25 (22) . https://dx.doi.org/10.2174/0929867324666170223153509
DOI https://dx.doi.org/10.2174/0929867324666170223153509 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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