Zhang Libo, Xiao Ziyuan, Zhang Dexin, Yang Lixin, Yuan Ziyang, Wang Guodong, Rui Xue, Fu Qiang, Song Yong, Ren Ke, Qiao Haishi
Department of Blood Screening Laboratory, Nanjing Red Cross Blood Center, Nanjing 210009, China.
Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, China.
ACS Nano. 2024 Dec 17;18(50):34219-34234. doi: 10.1021/acsnano.4c11658. Epub 2024 Dec 4.
Inducing trained immunity in macrophages is an increasingly promising strategy for preventing cancer development. However, it has not been investigated whether trained immunity in tumor-associated macrophages (TAMs) can be initiated for antitumor applications. Here, we provide a practical strategy that utilizes the macrophage membrane (M) to camouflage Bacillus Calmette-Guérin (M@BCG), endowing it with the capability to selectively target tumors and efficiently induce trained immunity for TAMs. Using a mouse model of Lewis lung carcinoma, we show that the introduction of macrophage membrane increases BCG's accumulation in orthotopic lung cancer tissues compared with naked BCG. The superior tumor-targeting ability can augment BCG-mediated trained immunity in TAMs, leading to a robust activation of immune responses. Furthermore, macrophage depletion and adoptive transfer of BCG-trained TAM experiments demonstrate that the antitumor activity of M@BCG is dependent on the trained immunity of TAMs. More importantly, intravenous administration of M@BCG can synergistically reinforce the antitumor activity of immune checkpoint blockade without causing systemic toxicity. Taken together, our study demonstrates the successful initiation of trained immunity in TAMs using M@BCG, which exhibits prominent antitumor performance through immune activation.
在巨噬细胞中诱导训练有素的免疫是预防癌症发展的一种越来越有前景的策略。然而,肿瘤相关巨噬细胞(TAM)中的训练有素的免疫是否可以启动用于抗肿瘤应用尚未得到研究。在这里,我们提供了一种实用策略,即利用巨噬细胞膜(M)来伪装卡介苗(M@BCG),赋予其选择性靶向肿瘤并有效诱导TAM训练有素的免疫的能力。使用Lewis肺癌小鼠模型,我们表明与裸卡介苗相比,巨噬细胞膜的引入增加了卡介苗在原位肺癌组织中的积累。这种优越的肿瘤靶向能力可以增强卡介苗介导的TAM训练有素的免疫,从而导致免疫反应的强烈激活。此外,巨噬细胞耗竭和卡介苗训练的TAM过继转移实验表明,M@BCG的抗肿瘤活性依赖于TAM的训练有素的免疫。更重要的是,静脉注射M@BCG可以协同增强免疫检查点阻断的抗肿瘤活性,而不会引起全身毒性。综上所述,我们的研究证明了使用M@BCG成功启动了TAM中的训练有素的免疫,其通过免疫激活表现出突出的抗肿瘤性能。
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