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通过 ADCC 和 T 细胞增强,利用 CD70 mRNA-LNPs 提高 5T4 mRNA 疫苗在前列腺癌治疗中的效力

英文原题:Enhancing the potency of 5T4 mRNA vaccine by CD70 mRNA-LNPs through ADCC and T cell boosting in prostate cancer therapy.

PubMed 2025/07/18(内容时间) J Nanobiotechnology Q1 · IF 15(JCR 2025)

研究概要

这些结果表明,这种联合mRNA疫苗策略可能为前列腺癌提供更有效且持久的治疗,并且CD70 mRNA作为一种免疫激活剂,在癌症免疫治疗中具有更广泛的潜力。

研究思路结论见上方概要

前列腺癌仍然是一个重大的健康挑战,因为传统治疗在晚期阶段往往无法提供长期获益。本研究探索了mRNA疫苗作为新型治疗策略的潜力,特别关注通过脂质纳米颗粒(LNPs)递送的5T4和CD70 mRNA的组合。5T4在多种肿瘤中高表达,但在正常组织中表达极低,是免疫治疗的理想靶点。选择CD70是因为其能够增强T细胞激活并增强整体免疫反应。

我们的研究结果表明,5T4和CD70 mRNA-LNPs联合应用显著增强了体液免疫和细胞免疫,从而在前列腺癌小鼠模型中改善了肿瘤抑制效果并延长了生存期。在机制上,这些LNPs增强了免疫应答,包括5T4特异性抗体升高、CD8+ T细胞活性增强以及自然杀伤(NK)细胞更加活跃。

展开英文摘要原文

BACKGROUND: Prostate cancer remains a significant health challenge, as conventional treatments often fail to provide long-term benefits in the advanced stages. This study explored the potential of mRNA vaccines as novel therapeutic strategies, specifically focusing on the combination of 5T4 and CD70 mRNA delivered via lipid nanoparticles (LNPs). 5T4, which is highly expressed in various tumors but minimally expressed in normal tissues, is an ideal target for immunotherapy. CD70 was selected for its capacity to enhance T cell activation and augment the overall immune response. RESULTS: Our findings demonstrated that the combination of 5T4 and CD70 mRNA-LNPs significantly enhanced both humoral and cellular immunity, resulting in improved tumor suppression and prolonged survival in a prostate cancer mouse model. Mechanistically, these LNPs increased the immune responses, including elevated 5T4-specific antibodies, enhanced CD8 + T cell activity, and more active natural killer (NK) cells. CONCLUSIONS: These results suggest that this combined mRNA vaccine strategy may offer more effective and durable treatments for prostate cancer and that CD70 mRNA, as an immune activator, has broader potential for cancer immunotherapy.

论文信息

作者
Cao F、Xu Y、Guan Y、Zhang K、Qiu H、Xu Z、He Y、Xiao ZX
第一作者单位
Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.China
通讯作者单位
Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China. pangjun2@mail.sysu.edu.cn.China
期刊
Journal of nanobiotechnology2025 Jul 18
原文标识
PubMed 40676580 · DOI 10.1186/s12951-025-03607-4