免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Advances in mRNA-Based Melanoma Vaccines: A Narrative Review of Lipid Nanoparticle and Dendritic Cell Delivery Platforms.
Advances in mRNA-Based Melanoma Vaccines: A Narrative Review of Lipid Nanoparticle and Dendritic Cell Delivery Platforms.
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黑色素瘤仍然是全球最致命的皮肤恶性肿瘤之一,尽管全身治疗取得了进展,复发和治疗耐药仍然是常见的挑战。继COVID-19 mRNA疫苗取得成功之后,靶向黑色素瘤抗原的mRNA癌症疫苗已成为一个有前景的治疗方向。本综述总结了关于mRNA黑色素瘤疫苗的当前证据,重点关注两种领先的递送平台:脂质纳米颗粒(LNP)和树突状细胞(DC)疫苗。对2015年至2025年MEDLINE、Embase和Scopus的综合检索识别了评估mRNA疫苗构建体和递送策略的临床试验、临床前研究和综述文章。已完成的临床研究表明,个性化LNP配制的mRNA疫苗可以增强新抗原特异性T细胞反应并改善无复发生存期,尤其是在与免疫检查点抑制剂联合使用时。基于DC的mRNA疫苗也显示出强效的免疫原性,当DC成熟得到优化时可观察到更强的反应。正在进行的试验继续研究下一代LNP制剂、DC致敏策略和个性化新抗原方法。
总体而言,当前证据表明LNP和DC平台均可通过拓宽T细胞反应和增强检查点抑制来增强抗肿瘤免疫。持续改进递送载体、新抗原选择和大规模生产工艺对于实现mRNA疫苗在黑色素瘤中的全部临床潜力至关重要。
Melanoma remains one of the deadliest cutaneous malignancies worldwide, and despite advances in systemic therapy, recurrence and treatment resistance remain frequent challenges. Following the success of COVID-19 mRNA vaccines, mRNA-based cancer vaccines targeting melanoma antigens have emerged as a promising therapeutic direction. This review summarizes current evidence on mRNA melanoma vaccines, focusing on two leading delivery platforms: lipid nanoparticles (LNPs) and dendritic cell (DC) vaccines.
A comprehensive search of MEDLINE, Embase, and Scopus from 2015 to 2025 identified clinical trials, preclinical studies, and review articles evaluating mRNA vaccine constructs and delivery strategies. Completed clinical studies demonstrate that personalized LNP-formulated mRNA vaccines can enhance neoantigen-specific T-cell responses and improve recurrence-free survival, particularly when combined with immune checkpoint inhibitors.
DC-based mRNA vaccines also show potent immunogenicity, with stronger responses observed when DC maturation is optimized. Ongoing trials continue to investigate next-generation LNP formulations, DC priming strategies, and personalized neoantigen approaches.
Overall, current evidence indicates that both LNP and DC platforms can augment antitumor immunity by broadening T-cell responses and enhancing checkpoint inhibition. Continued refinement of delivery vehicles, neoantigen selection, and scalable manufacturing processes will be essential to realizing the full clinical potential of mRNA vaccines in melanoma.
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