Liu Bin, Zhou Jia, He Wei, Xie Bo, Zhang Rui, Cheng Xiaocheng, Zhang Yueming, Xu Li, Guo Shuliang
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Chongqing Medical University, Youyi Rd 1, Yuzhong, 400016, Chongqing, China.
Department of Pulmonary and Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, No. 116, Changjiang South Road, Tianyuan District, Zhuzhou, 412007, Hunan, China.
Discov Oncol. 2025 Apr 26;16(1):621. doi: 10.1007/s12672-025-02398-2.
Despite advancements in systemic chemotherapy and immune checkpoint inhibitors (ICIs), advanced non-small cell lung cancer (NSCLC) continues to exhibit poor prognosis, underscoring an urgent need for safer and more effective therapeutic strategies. This study investigates the safety profile and biological effects of bronchial arterial infusion (BAI)-administered anti-PD-1 monoclonal antibody (aPD-1 mAb) using a preclinical beagle model and a clinical cohort of advanced NSCLC patients.
In preclinical evaluations, male beagles (n = 3/group) were randomized to receive 5 mg/kg aPD-1 mAb via BAI or intravenous routes (Venous group). Safety assessments included longitudinal imaging, biochemical analyses, and histopathological evaluation. Clinically, patients with advanced NSCLC meeting stringent inclusion criteria underwent BAI immunotherapy, with systematic monitoring of adverse events (AEs).
Both administration routes demonstrated comparable safety in canines, with no evidence of immune-related pneumonitis or structural lung alterations on CT or histology. Transient AEs (e.g., hematoma, lameness) resolved spontaneously. Pharmacokinetic analysis revealed similar systemic drug concentrations and tissue distribution between BAI and Venous groups (all p > 0.05). Biochemical profiling identified isolated mild LDH elevation in one BAI-treated canine. Notably, the BAI group exhibited significantly enhanced systemic IL-2 levels (80.15 ± 5.24 pg/mL vs. 66.47 ± 5.24 pg/mL in Venous groups, p = 0.001) at day 28, paralleled by elevated pulmonary IL-2 expression (626.90 ± 18.49 vs. 559.18 ± 45.61 pg/mg, p = 0.03). In the clinical cohort (n = 17; 94.1% male, mean age 61.6 ± 7.1 years), BAI immunotherapy was well-tolerated with mild AEs including nausea (n = 1), dyspnea (n = 1), atrial fibrillation (n = 1), and puncture-site hematoma (n = 1). No severe immune-related toxicities (e.g., pneumonitis) emerged during follow-up.
Our study suggest the preliminary safety and feasibility of delivering aPD-1 mAb via BAI in both canine models and NSCLC patients.
尽管全身化疗和免疫检查点抑制剂（ICI）取得了进展，但晚期非小细胞肺癌（NSCLC）的预后仍然很差，这突出表明迫切需要更安全、更有效的治疗策略。本研究使用临床前比格犬模型和晚期NSCLC患者的临床队列，研究支气管动脉灌注（BAI）给予抗PD-1单克隆抗体（aPD-1 mAb）的安全性和生物学效应。
在临床前评估中，将雄性比格犬（每组n = 3）随机分为通过BAI或静脉途径接受5 mg/kg aPD-1 mAb的组（静脉组）。安全性评估包括纵向成像、生化分析和组织病理学评估。在临床上，符合严格纳入标准的晚期NSCLC患者接受BAI免疫治疗，并系统监测不良事件（AE）。
两种给药途径在犬类中显示出相当的安全性，CT或组织学上均无免疫相关肺炎或肺部结构改变的证据。短暂的AE（如血肿、跛行）可自发缓解。药代动力学分析显示BAI组和静脉组之间的全身药物浓度和组织分布相似（所有p>0.05）。生化分析确定在一只接受BAI治疗的犬中出现孤立的轻度乳酸脱氢酶升高。值得注意的是，在第28天，BAI组的全身IL-2水平显著升高（80.15±5.24 pg/mL，静脉组为66.47±5.24 pg/mL，p = 0.001），同时肺部IL-2表达升高（626.90±18.49对559.18±45.61 pg/mg，p = 0.03）。在临床队列（n = 17；94.1%为男性，平均年龄61.6±7.1岁）中，BAI免疫治疗耐受性良好，轻度AE包括恶心（n = 1）、呼吸困难（n = 1）、心房颤动（n = 1）和穿刺部位血肿（n = 1）。随访期间未出现严重的免疫相关毒性（如肺炎）。
我们的研究表明，在犬类模型和NSCLC患者中，通过BAI给予aPD-1 mAb具有初步的安全性和可行性。
Zotero 插件
