Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion

被引：184

作者：

Guo, Mengfei ^{[1
]}

Wu, Feng ^{[1
]}

Hu, Guorong ^{[1
]}

Chen, Lian ^{[1
]}

Xu, Juanjuan ^{[1
]}

Xu, Pingwei ^{[2
]}

Wang, Xuan ^{[1
]}

Li, Yumei ^{[1
]}

Liu, Shuqing ^{[1
]}

Zhang, Shuai ^{[1
]}

Huang, Qi ^{[1
]}

Fan, Jinshuo ^{[1
]}

Lv, Zhilei ^{[1
]}

Zhou, Mei ^{[1
]}

Duan, Limin ^{[1
]}

Liao, Tingting ^{[1
]}

Yang, Guanghai ^{[3
]}

Tang, Ke ^{[2
]}

Liu, Bifeng ^{[4
]}

Liao, Xiaofei ^{[5
]}

Tao, Xiaonan ^{[1
]}

Jin, Yang ^{[1
]}

机构：

[1] Huazhong Univ Sci & Technol, Key Lab Pulm Dis, Dept Resp & Crit Care Med, Union Hosp,Tongji Med Coll,Hlth Minist, Wuhan 430022, Hubei, Peoples R China

[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan 430030, Hubei, Peoples R China

[3] Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Thorac Surg, Wuhan 430022, Hubei, Peoples R China

[4] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Dept Biomed Engn, Syst Biol Theme, Wuhan 430074, Hubei, Peoples R China

[5] Huazhong Univ Sci & Technol, Sch Comp Sci & Technol, Wuhan 430074, Hubei, Peoples R China

来源：

SCIENCE TRANSLATIONAL MEDICINE | 2019年 / 11卷 / 474期

基金：

中国国家自然科学基金;

关键词：

EXTRACELLULAR VESICLES; DENDRITIC CELLS; CHEST TUBE; SURVIVAL; DELIVERY; MACROPHAGES; EXOSOMES; NANOPARTICLES; MICROVESICLES; RESISTANCE;

D O I：

10.1126/scitranslmed.aat5690

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Cell membrane-derived microparticles (MPs), the critical mediators of intercellular communication, have gained much interest for use as natural drug delivery systems. Here, we examined the therapeutic potential of tumor cell-derived MPs (TMPs) in the context of malignant pleural effusion (MPE). TMPs packaging the chemotherapeutic drug methotrexate (TMPs-MTX) markedly restricted MPE growth and provided a survival benefit in MPE models induced by murine Lewis lung carcinoma and colon adenocarcinoma cells. On the basis of the potential benefit and minimal toxicity of TMPs-MIX, we conducted a human study of intrapleural delivery of a single dose of autologous TMPs packaging methotrexate (ATMPs-MTX) to assess their safety, immunogenicity, and clinical activity. We report our findings on 11 advanced lung cancer patients with MPE. We found that manufacturing and infusing ATMPs-MTX were feasible and safe, without evidence of toxic effects of grade 3 or higher. Evaluation of the tumor microenvironment in MPE demonstrated notable reductions in tumor cells and CD163(+) macrophages in MPE after ATMP-MTX infusion, which then translated into objective clinical responses. Moreover, ATMP-MTX treatment stimulated CD4(+) T cells to release IL-2 and CD8(+) cells to release IFN-gamma. Our initial experience with ATMPs-MTX in advanced lung cancer with MPE suggests that ATMPs targeting malignant cells and the immunosuppressive microenvironment may be a promising therapeutic platform for treating malignancies.

引用

页数：15

共 61 条

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