Autologous tumor cell–derived microparticle-based targeted chemotherapy in lung cancer patients with malignant pleural effusion
Menée à l'aide de modèles murins et auprès de 11 patients atteints d'un cancer du poumon de stade avancé avec épanchement pleural, cette étude analyse la toxicité, l'immunogénicité et les effets thérapeutiques de microparticules dérivées de cellules tumorales autologues et transportant du méthotrexate
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.