Department of Nuclear Medicine, the Fourth Hospital of Harbin Medical University, Harbin, China.
NHC Key Laboratory of Molecular Probe and Targeted Diagnosis and Therapy, Molecular Imaging Research Center (MIRC) of Harbin Medical University, Harbin, China.
Sci Adv. 2024 Nov 29;10(48):eadp7561. doi: 10.1126/sciadv.adp7561.
The currently available immune checkpoint inhibitors (ICIs) often fail to achieve the desired clinical outcomes due to inadequate immune activation, particularly in patients with lung cancer. To reverse this situation, we synthesized inhalable PFCE-C25 nanoemulsions (NEs), which target lymphocyte activation genes (LAG-3) on immune cells within tumor microenvironment and tumor-draining lymph nodes (TDLNs). By combining in vivo F-MR molecular imaging, we investigate the immunological effects of a single low-dose PFCE-C25 NEs in multiple murine lung cancer models, including human immune system (HIS) mouse models, and validated its immunological effects in human TDLNs. The nebulization therapy with PFCE-C25 NEs demonstrated a notable and enduring maturation of dendritic cells (DCs) in TDLNs, leading to systemic immune responses, prolonged survival, the establishment of immune memory, and resistance to tumor rechallenge. Thus, PFCE-C25 NEs successfully demonstrate a promising and efficient approach for enhancing lymphatic transport and sustained activation of antitumor immune responses in lung cancer.
目前可用的免疫检查点抑制剂（ICIs）由于免疫激活不足，往往无法达到预期的临床效果，尤其是在肺癌患者中。为了改变这种情况，我们合成了可吸入的 PFCE-C25 纳米乳液（NE），该乳液针对肿瘤微环境和肿瘤引流淋巴结（TDLNs）内免疫细胞上的淋巴细胞激活基因（LAG-3）。通过结合体内 F-MR 分子成像，我们研究了单次低剂量 PFCE-C25 NE 在多种小鼠肺癌模型中的免疫效果，包括人免疫系统（HIS）小鼠模型，并在人 TDLNs 中验证了其免疫效果。PFCE-C25 NE 的雾化治疗在 TDLNs 中显著且持久地成熟树突状细胞（DC），引发全身免疫反应、延长生存时间、建立免疫记忆和抵抗肿瘤再挑战。因此，PFCE-C25 NE 成功地展示了一种有前途且有效的方法，可增强肺癌中淋巴转运和持续激活抗肿瘤免疫反应的能力。
