Huang Yucheng, Su Miao, Lin Weihuan, Zhang Peirong, Hou Hengliang, Zeng Fanjun, Huang Luyu, Li Qiaxuan, Deng Jialong, Liu Shengbo, Qiu Hongrui, Yuan Xiaoqing, Peng Li, Xu Bin, Zhou Haiyu
School of Medicine, South China University of Technology, Guangzhou, 510006, P. R. China.
Department of Thoracic Surgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510080, P. R. China.
Theranostics. 2025 Jul 2;15(15):7677-7692. doi: 10.7150/thno.114347. eCollection 2025.
Tumor vaccines that combine tumor antigens with immune adjuvants offer a promising strategy for cancer immunotherapy. A particularly effective approach involves the generation of tumor antigens within the tumor microenvironment and their subsequent delivery to the lymph nodes alongside immune adjuvants. However, Co-delivery of antigen and adjuvant on a single nano-platform remains facing some key problems, such as a single nanomedicine cannot simultaneously achieve antigen production, capture, and delivery to lymph nodes, as well as leakage of adjuvant due to destruction of nano-drug by exogenous stimuli and failure to capture antigen effectively. To address this, this study develops two synergistic nanodrugs: AuP and VNP. Under 1064 nm laser irradiation, AuP generates many tumor antigens, whereas VNP, distinguished by its small size and high viscosity, captures these autologous antigens and encapsulates the immune adjuvant R848. This combination creates an cancer nanovaccine capable of lymph node migration. Nanovaccines enhance dendritic cell uptake and maturation, promoting antigen processing and presentation to T cells, which triggers a robust antitumor immune response. Remarkably, the nanovaccine we developed demonstrated superior therapeutic efficacy in distal tumors, postoperative recurrence and pulmonary metastatic tumor models, while also inducing long-term immune memory. This study presents a straightforward and effective strategy for developing in situ nanovaccines for cancer immunotherapy, with wide-ranging clinical application prospects.
将肿瘤抗原与免疫佐剂相结合的肿瘤疫苗为癌症免疫治疗提供了一种很有前景的策略。一种特别有效的方法是在肿瘤微环境中产生肿瘤抗原，随后将其与免疫佐剂一起递送至淋巴结。然而，在单个纳米平台上共同递送抗原和佐剂仍然面临一些关键问题，例如单一纳米药物无法同时实现抗原的产生、捕获以及递送至淋巴结，并且由于外源性刺激导致纳米药物破坏，佐剂会泄漏，无法有效捕获抗原。为了解决这一问题，本研究开发了两种协同纳米药物：AuP和VNP。在1064nm激光照射下，AuP产生许多肿瘤抗原，而VNP以其小尺寸和高粘度为特征，捕获这些自体抗原并封装免疫佐剂R848。这种组合产生了一种能够迁移至淋巴结的癌症纳米疫苗。纳米疫苗增强树突状细胞摄取和成熟，促进抗原加工并呈递给T细胞，从而触发强大的抗肿瘤免疫反应。值得注意的是，我们开发的纳米疫苗在远端肿瘤、术后复发和肺转移瘤模型中显示出卓越的治疗效果，同时还能诱导长期免疫记忆。本研究为开发用于癌症免疫治疗的原位纳米疫苗提出了一种直接有效的策略，具有广泛的临床应用前景。
