T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics

Liao，Jianhong1; Pan，Hong1; Huang，Guojun1; Gong，Han1; Chen，Ze1; Yin，Ting1; Zhang，Baozhen1; Chen，Tingtao4; Zheng，Mingbin1,3; Cai，Lintao1,2

2024-04-23

10.1016/j.celrep.2024.114086

Cell Reports   影响因子和分区

2211-1247

Immune checkpoint blockade (ICB) has revolutionized cancer therapy but only works in a subset of patients due to the insufficient infiltration, persistent exhaustion, and inactivation of T cells within a tumor. Herein, we develop an engineered probiotic (interleukin [IL]-12 nanoparticle Escherichia coli Nissle 1917 [INP-EcN]) acting as a living drug factory to biosynthesize anti-PD-1 and release IL-12 for initiating systemic antitumor immunity through T cell cascade regulation. Mechanistically, INP-EcN not only continuously biosynthesizes anti-PD-1 for relieving immunosuppression but also effectively cascade promote T cell activation, proliferation, and infiltration via responsive release of IL-12, thus reaching a sufficient activation threshold to ICB. Tumor targeting and colonization of INP-EcNs dramatically increase local drug accumulations, significantly inhibiting tumor growth and metastasis compared to commercial inhibitors. Furthermore, immune profiling reveals that anti-PD-1/IL-12 efficiently cascade promote antitumor effects in a CD8 T cell-dependent manner, clarifying the immune interaction of ICB and cytokine activation. Ultimately, such engineered probiotics achieve a potential paradigm shift from T cell exhaustion to activation and show considerable promise for antitumor bio-immunotherapy.

anti-PD-1 CP: Cancer engineered probiotics immune cascade regulation interleukin-12 living drug factory

SCI

英语

其他

2-s2.0-85189810754

Scopus

1.Guangdong Key Laboratory of Nanomedicine,CAS-HK Joint Lab of Biomaterials,CAS Key Laboratory of Biomedical Imaging Science and System,Institute of Biomedicine and Biotechnology,Shenzhen Institute of Advanced Technology (SIAT),Chinese Academy of Sciences (CAS),Shenzhen,518055,China
2.Sino-Euro Center of Biomedicine and Health,Luohu Shenzhen,518024,China
3.National Clinical Research Center for Infectious Disease,Shenzhen Third People's Hospital,The Second Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518112,China
4.National Engineering Research Center for Bioengineering Drugs and the Technologies,Institute of Translational Medicine,Nanchang University,Nanchang,330031,China

Liao，Jianhong,Pan，Hong,Huang，Guojun,et al. T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics[J]. Cell Reports,2024,43(4).

Liao，Jianhong.,Pan，Hong.,Huang，Guojun.,Gong，Han.,Chen，Ze.,...&Cai，Lintao.(2024).T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics.Cell Reports,43(4).

Liao，Jianhong,et al."T cell cascade regulation initiates systemic antitumor immunity through living drug factory of anti-PD-1/IL-12 engineered probiotics".Cell Reports 43.4(2024).