He Jia, Wang Chaoyu, Fang Xiao, Li Junyao, Shen Xueying, Zhang Junxia, Peng Cheng, Li Hongjian, Li Sai, Karp Jeffrey M, Kuai Rui
School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
Tsinghua-Peking Center for Life Sciences, Beijing, China.
Nat Commun. 2024 Sep 16;15(1):8121. doi: 10.1038/s41467-024-52104-z.
Inducing high levels of antigen-specific CD8α T cells in the tumor is beneficial for cancer immunotherapy, but achieving this in a safe and effective manner remains challenging. Here, we have developed a designer liposomal nanovaccine containing a sonosensitizer (LNVS) to efficiently program T cell immunity in mice. Following intravenous injection, LNVS accumulates in the spleen in a protein corona and fluidity-dependent manner, leading to greater frequencies of antigen-specific CD8α T cells than soluble vaccines (the mixture of antigens and adjuvants). Meanwhile, some LNVS passively accumulates in the tumor, where it responds to ultrasound (US) to increase the levels of chemokines and adhesion molecules that are beneficial for recruiting CD8α T cells to the tumor. LNVS + US induces higher levels of intratumoral antitumor T cells than traditional sonodynamic therapy, regresses established mouse MC38 tumors and orthotopic cervical cancer, and protects cured mice from relapse. Our platform sheds light on the importance of tuning the fluidity and protein corona of naovaccines to program T cell immunity in mice and may inspire new strategies for cancer immunotherapy.
在肿瘤中诱导高水平的抗原特异性CD8α T细胞对癌症免疫治疗有益，但以安全有效的方式实现这一点仍然具有挑战性。在这里，我们开发了一种含有声敏剂的定制脂质体纳米疫苗（LNVS），以有效地在小鼠中编程T细胞免疫。静脉注射后，LNVS以蛋白质冠层和流动性依赖的方式在脾脏中积累，导致抗原特异性CD8α T细胞的频率高于可溶性疫苗（抗原和佐剂的混合物）。同时，一些LNVS被动地在肿瘤中积累，在那里它对超声（US）作出反应，以增加趋化因子和粘附分子的水平，这有利于将CD8α T细胞招募到肿瘤中。与传统的声动力疗法相比，LNVS + US诱导更高水平的肿瘤内抗肿瘤T细胞，使已建立的小鼠MC38肿瘤和原位宫颈癌消退，并保护治愈的小鼠免于复发。我们的平台揭示了调节纳米疫苗的流动性和蛋白质冠层以在小鼠中编程T细胞免疫的重要性，并可能激发癌症免疫治疗的新策略。
