Research ArticleCancer

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

See allHide authors and affiliations

Science Translational Medicine  09 Jan 2019:
Vol. 11, Issue 474, eaat5690
DOI: 10.1126/scitranslmed.aat5690

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Insider attack on tumors

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.

Abstract

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.

View Full Text