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

作者：Guo, Mengfei; Wu, Feng; Hu, Guorong; Chen, Lian; Xu, Juanjuan; Xu, Pingwei; Wang, Xuan; Li, Yumei; Liu, Shuqing; Zhang, Shuai; Huang, Qi; Fan, Jinshuo; Lv, Zhilei; Zhou, Mei; Duan, Limin; Liao, Tingting; Yang, Guanghai; Tang, Ke; Liu, Bifeng; Liao, Xiaofei; Tao, Xiaonan; Jin, Yang^*

来源：Science Translational Medicine, 2019, 11(474): eaat5690.

DOI：10.1126/scitranslmed.aat5690

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

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.

• 出版日期2019-1-9
• 单位华中科技大学