RT Journal Article
SR Electronic
T1 Autologous tumor cell–derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion
JF Science Translational Medicine
FD American Association for the Advancement of Science
SP eaat5690
DO 10.1126/scitranslmed.aat5690
VO 11
IS 474
A1 Guo, Mengfei
A1 Wu, Feng
A1 Hu, Guorong
A1 Chen, Lian
A1 Xu, Juanjuan
A1 Xu, Pingwei
A1 Wang, Xuan
A1 Li, Yumei
A1 Liu, Shuqing
A1 Zhang, Shuai
A1 Huang, Qi
A1 Fan, Jinshuo
A1 Lv, Zhilei
A1 Zhou, Mei
A1 Duan, Limin
A1 Liao, Tingting
A1 Yang, Guanghai
A1 Tang, Ke
A1 Liu, Bifeng
A1 Liao, Xiaofei
A1 Tao, Xiaonan
A1 Jin, Yang
YR 2019
UL http://stm.sciencemag.org/content/11/474/eaat5690.abstract
AB A major factor that limits the effectiveness of cancer therapy is the ability to get the treatment to tumor cells. A variety of microparticles and nanoparticles have been developed in the past, and each of them has its own advantages and limitations. Guo et al. have now developed a method of creating microparticles from the patients’ own cancer cells, resulting in improved intratumoral delivery. The authors embedded the chemotherapy drug methotrexate inside the microparticles and then successfully tested this approach in both mouse models and patients with pleural effusions caused by lung cancer.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-MTX, 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-γ. 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.