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Published on: November 10, 2023
Autologous tumor cell-derived microparticle-based targeted chemotherapy in lung cancer patients with malignant
Mengfei Guo1, Feng Wu1, Guorong Hu1
1Key Laboratory of Pulmonary Diseases of Health Ministry, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
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.
Insights
Tumor cell-derived microparticles (TMPs) loaded with methotrexate (MTX) showed promise in treating malignant pleural effusion (MPE). This approach was safe and effective in advanced lung cancer patients, reducing tumors and improving immune response.
Area of Science:
- Oncology
- Nanomedicine
- Immunology
Background:
- Cell membrane-derived microparticles (MPs) are key in intercellular communication and show potential as drug delivery systems.
- Tumor cell-derived MPs (TMPs) packaging methotrexate (TMPs-MTX) demonstrated efficacy in restricting malignant pleural effusion (MPE) growth and improving survival in preclinical models.
- Minimal toxicity observed with TMPs-MTX warranted further investigation in human subjects.
Purpose of the Study:
- To assess the safety, immunogenicity, and clinical activity of intrapleural delivery of autologous TMPs packaging methotrexate (ATMPs-MTX) in advanced lung cancer patients with MPE.
- To evaluate the impact of ATMPs-MTX on the tumor microenvironment and immune cell responses.
Main Methods:
- A human study involving 11 advanced lung cancer patients with MPE receiving a single intrapleural dose of autologous TMPs-MTX.
- Manufacturing and infusion feasibility and safety assessment of ATMPs-MTX.
- Evaluation of tumor cell and immune cell populations (CD163+ macrophages, CD4+ and CD8+ T cells) in MPE post-treatment.
- Assessment of cytokine release (IL-2, IFN-γ) from T cells.
Main Results:
- Manufacturing and infusion of ATMPs-MTX were feasible and safe, with no grade 3 or higher toxic effects observed.
- Significant reductions in MPE tumor cells and CD163+ macrophages were noted post-infusion.
- ATMP-MTX treatment stimulated CD4+ T cells to release IL-2 and CD8+ T cells to release IFN-γ.
- Objective clinical responses were observed in patients.
Conclusions:
- Autologous TMPs-MTX represent a feasible and safe therapeutic platform for advanced lung cancer with MPE.
- ATMPs-MTX effectively target malignant cells and the immunosuppressive tumor microenvironment.
- This approach holds promise for treating various malignancies by modulating the immune response.
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