Cao Fei, Xu Yuandong, Guan Yupeng, Zhang Kexin, Qiu Haowei, Xu Zhen, He Yunru, Xiao Ze Xiu, Zha Gao-Feng, Pang Jun
Department of Urology, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
Scientific Research Center, the Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, 518107, Guangdong, China.
J Nanobiotechnology. 2025 Jul 18;23(1):523. doi: 10.1186/s12951-025-03607-4.
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.
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.
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.
前列腺癌仍然是一项重大的健康挑战，因为传统治疗方法在晚期往往无法提供长期益处。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（LNP）递送的5T4和CD70 mRNA的组合。5T4在各种肿瘤中高度表达，但在正常组织中表达极少，是免疫治疗的理想靶点。选择CD70是因为它具有增强T细胞活化和增强整体免疫反应的能力。
我们的研究结果表明，5T4和CD70 mRNA-LNP的组合显著增强了体液免疫和细胞免疫，在前列腺癌小鼠模型中导致更好的肿瘤抑制和更长的生存期。从机制上讲，这些LNP增强了免疫反应，包括升高5T4特异性抗体、增强CD8 T细胞活性和更活跃的自然杀伤（NK）细胞。
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和持久的治疗，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。
