Grupo de Genética de Micobacterias, Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Facultad de Medicina, Universidad de Zaragoza, IIS-Aragon, Zaragoza, Spain.
CIBER Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain.
Nat Commun. 2023 Oct 4;14(1):6090. doi: 10.1038/s41467-023-41768-8.
Intravesical administration of Bacillus Calmette-Guérin (BCG) was one of the first FDA-approved immunotherapies and remains a standard treatment for bladder cancer. Previous studies have demonstrated that intravenous (IV) administration of BCG is well-tolerated and effective in preventing tuberculosis infection in animals. Here, we examine IV BCG in several preclinical lung tumor models. Our findings demonstrate that BCG inoculation reduced tumor growth and prolonged mouse survival in models of lung melanoma metastasis and orthotopic lung adenocarcinoma. Moreover, IV BCG treatment was well-tolerated with no apparent signs of acute toxicity. Mechanistically, IV BCG induced tumor-specific CD8 T cell responses, which were dependent on type 1 conventional dendritic cells, as well as NK cell-mediated immunity. Lastly, we also show that IV BCG has an additive effect on anti-PD-L1 checkpoint inhibitor treatment in mouse lung tumors that are otherwise resistant to anti-PD-L1 as monotherapy. Overall, our study demonstrates the potential of systemic IV BCG administration in the treatment of lung tumors, highlighting its ability to enhance immune responses and augment immune checkpoint blockade efficacy.
卡介苗（BCG）的膀胱内给药是 FDA 批准的首批免疫疗法之一，目前仍是膀胱癌的标准治疗方法。先前的研究表明，BCG 的静脉内（IV）给药在预防动物结核感染方面耐受良好且有效。在这里，我们在几种临床前肺肿瘤模型中检查了 IV BCG。我们的研究结果表明，BCG 接种可减少肺黑色素瘤转移和原位肺腺癌模型中的肿瘤生长并延长小鼠的存活期。此外，IV BCG 治疗耐受良好，没有明显的急性毒性迹象。从机制上讲，IV BCG 诱导了肿瘤特异性 CD8+T 细胞反应，该反应依赖于 1 型传统树突状细胞以及 NK 细胞介导的免疫。最后，我们还表明，在对 PD-L1 检查点抑制剂单药治疗耐药的小鼠肺肿瘤中，IV BCG 与抗 PD-L1 检查点抑制剂治疗具有协同作用。总体而言，我们的研究表明，全身 IV BCG 给药在治疗肺肿瘤方面具有潜力，突出了其增强免疫反应和增强免疫检查点阻断功效的能力。
