北京大学周德敏课题组设计了一种为肺癌疫苗提供抗原的工程流感病毒。相关论文于2023年5月25日发表在《自然—生物技术》杂志上。

他们在黑色素瘤模型中使用模型抗原卵清蛋白(OVA)，展示了一种嵌合抗原肽流感病毒(CAP-Flu)系统，用于将与甲型流感病毒(IAV)结合的抗原肽递送到肺部。他们将减毒IAV与先天免疫刺激剂CpG结合，经鼻给药小鼠肺后，观察到肿瘤免疫细胞浸润增加。然后用点击化学将OVA共价显示在IAV-CPG上。与单独使用多肽相比，这种结构的疫苗接种产生了强大的树突状细胞抗原摄取，特异性免疫细胞反应和肿瘤浸润淋巴细胞的显著增加。

最后，研究人员设计了IAV来表达抗PD1-L1纳米体，进一步增强肺转移灶的消退，延长小鼠再攻击后的生存期。工程化的IAV可以与任何感兴趣的肿瘤新抗原结合以产生肺癌疫苗。

据悉，促进抗肿瘤免疫反应的癌症新抗原疫苗的发展，在一定程度上受到新抗原递送到肿瘤的挑战的阻碍。

附：英文原文

Title: An engineered influenza virus to deliver antigens for lung cancer vaccination

Author: Ji, Dezhong, Zhang, Yuanjie, Sun, Jiaqi, Zhang, Bo, Ma, Wenxiao, Cheng, Boyang, Wang, Xinchen, Li, Yuanhao, Mu, Yu, Xu, Huan, Wang, Qi, Zhang, Chuanling, Xiao, Sulong, Zhang, Lihe, Zhou, Demin

Issue&Volume: 2023-05-25

Abstract: The development of cancer neoantigen vaccines that prime the anti-tumor immune responses has been hindered in part by challenges in delivery of neoantigens to the tumor. Here, using the model antigen ovalbumin (OVA) in a melanoma model, we demonstrate a chimeric antigenic peptide influenza virus (CAP-Flu) system for delivery of antigenic peptides bound to influenza A virus (IAV) to the lung. We conjugated attenuated IAVs with the innate immunostimulatory agent CpG and, after intranasal administration to the mouse lung, observed increased immune cell infiltration to the tumor. OVA was then covalently displayed on IAV-CPG using click chemistry. Vaccination with this construct yielded robust antigen uptake by dendritic cells, a specific immune cell response and a significant increase in tumor-infiltrating lymphocytes compared to peptides alone. Lastly, we engineered the IAV to express anti-PD1-L1 nanobodies that further enhanced regression of lung metastases and prolonged mouse survival after rechallenge. Engineered IAVs can be equipped with any tumor neoantigen of interest to generate lung cancer vaccines.

DOI: 10.1038/s41587-023-01796-7

Source: https://www.nature.com/articles/s41587-023-01796-7