腺病毒组装的DC疫苗能够诱导双重靶向肿瘤抗原和腺病毒的CTLs，以消灭肿瘤。
Adenovirus-assembled DC vaccine induces dual-targeting CTLs for tumor antigen and adenovirus to eradicate tumors.
发表日期：2023 Aug 11
作者：
Jiage Ding, Yanyan Zheng, Fei Zhu, Meng Wang, Lin Fang, Huizhong Li, Hui Tian, Yong Liu, Gang Wang, Junnian Zheng, Dafei Chai
来源：
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要：
树突状细胞（DC）疫苗是一种有前景的肿瘤免疫治疗策略，但在治疗固体肿瘤方面其疗效有限。为了克服这一局限性，研制了一个肿瘤溶解性腺病毒（OAV-IL-12），以增强腺病毒组装的树突状细胞疫苗（DCs-CD137L/CAIX）的抗原靶向能力，用于肾癌治疗。OAV-IL-12的肿瘤周围给药增加了浸润肿瘤的DCs以及它们的亚群（CD8+DCs和CD103+DCs）。OAV-IL-12与DCs-CD137L/CAIX的联合应用通过诱导强效细胞毒性T淋巴细胞（CTL）效应和改善肿瘤病灶内的免疫浸润，显著抑制了皮下肿瘤的生长。有意思的是，该治疗还通过引发全身性CTL反应，减少了注射OAV-IL-12一侧远离病灶的肿瘤生长。此外，OAV-IL-12还增强了DCs-CD137L/CAIX治疗对CAIX和腺病毒抗原的双重CTL反应。该治疗方法的治疗效益主要依赖于多功能CD8+T细胞免疫反应，如耗尽实验所示。此外，OAV-IL-12增强的DCs-CD137L/CAIX治疗通过诱导记忆性CD8+T细胞免疫反应产生了持久的抗肿瘤保护效应。这些结果表明，在OAV-IL-12的增强下，基于腺病毒的树突状细胞疫苗对肾癌和其他实体肿瘤的有效靶向治疗方法具有潜力。版权所有 © 2023 Elsevier B.V. 保留所有权利。
The dendritic cell (DC) vaccine is a promising cancerimmunotherapy strategy, but its efficacy in treating the solid tumor is limited. To overcome this limitation, an oncolytic adenovirus (OAV-IL-12) was developed to enhance antigen targeting ability of adenovirus-assembled DC vaccine (DCs-CD137L/CAIX) for renal carcinoma treatment. Peritumoral administration of OAV-IL-12 increased the number of tumor-infiltrating DCs and their subsets (CD8+DCs and CD103+DCs). Combining OAV-IL-12 with DCs-CD137L/CAIX significantly inhibited the growth of subcutaneous tumors by inducing potent cytotoxic T lymphocyte (CTL) effect and improving the immune infiltration in tumor lesions. Interestingly, this treatment also reduced tumor growth distal to the OAV-IL-12 injecting side via eliciting a systemic CTL response. Furthermore, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment induced dual CTL responses against both CAIX and adenovirus antigens. The therapeutic benefits of this treatment approach mainly relied on multifunctional CD8+T cell immune responses, as indicated by the depletion assay. Moreover, OAV-IL-12 potentiated DCs-CD137L/CAIX treatment generated a long-lasting protective effect against tumors by inducing memory CD8+T cell immune responses. These results suggest that the effective tumor targeting of the adenovirus-based DC vaccine, boosted by OAV-IL-12, is a promising treatment approach for renal carcinoma and other solid tumors.Copyright © 2023 Elsevier B.V. All rights reserved.