ArticleProceedings of the National Academy of Sciences of the United States of America2025
In vivo generation of CAR macrophages via the enucleated mesenchymal stem cell delivery system for glioblastoma therapy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed.
- Organization from cell to tissue derived delivery systems for immunotherapy.Materials today. Bio · 2026Article
- A narrative review of barrier-matched engineering of macrophages for solid tumor immunotherapy: design logic, translational barriers and clinical outlook.Translational cancer research · 2026Review
- Cell-based cancer immunotherapy: milestones, mechanistic insights, and emerging therapeutic directions.Acta pharmacologica Sinica · 2026Review
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- Advances in Living Cell-Mediated Nanodrug Delivery Systems: Construction Strategies, Applications and Challenges.Pharmaceutics · 2026Review
- In vivo CAR-M therapy: advancing precision delivery and programmable immune remodeling.Cell communication and signaling : CCS · 2026Review
- Deformability-augmented mesenchymal stem cells post-enucleation for efficient mRNA intervention of pulmonary fibrosis in rodent model.iScience · 2026Article
- CAR-neutrophils produced in vivo to treat glioma.Nature biomedical engineering · 2026Article
- Consensus statement on microglial and macrophage functions in gliomas.Acta neuropathologica · 2026Review
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- NG2-targeting macrophages inhibit 3D invasion of patient-derived glioblastoma spheroids.bioRxiv : the preprint server for biology · 2026Article
- Antibody-dependent cellular phagocytosis in cancer immunotherapy: research and perspectives.Journal of translational medicine · 2026Review
- Beyond CAR-T and oncology: broadening chimeric antigen receptor technologies across cell types and diseases.Precision clinical medicine · 2026Review
- Engineering macrophages for effective and safe targeting of CD47 cancer cells in the tumor microenvironment.Journal for immunotherapy of cancer · 2026Article
- CAR-macrophages: a new chapter in cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Article
- In vivo engineering of CAR-T cells: delivery strategies and clinical translation.Biomarker research · 2026Review
- Cellular Allies Against Glioblastoma: Therapeutic Potential of Macrophages and Mesenchymal Stromal Cells.Pharmaceutics · 2026Review
- Innate immune cells in chimeric antigen receptor therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- The role of macrophages in radiation-induced lung injury: from pathological mechanisms to therapeutic targets.Frontiers in immunology · 2026Review
- Engineered nanomedicine remodels the postoperative cavity microenvironment to suppress glioblastoma recurrence.Theranostics · 2026Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Glioblastoma multiforme (GBM) is one of the most aggressive intracranial tumors for which there is no effective treatment. Chimeric antigen receptor macrophage (CAR-M) therapies have demonstrated impressive therapeutic efficacy in solid tumors; however, the cost and rigor associated with manufacturing engineered macrophages ex vivo can be prohibitive. Here, we utilized enucleated mesenchymal stem cells (MSCs) as vehicles for the targeted delivery of CAR-encoding plasmid to reprogram glioma-associated microglia/macrophages (GAM), thereby achieving CAR-M preparation in vivo. Specifically, we observed that the enucleated cells retained the key organelle function and membrane integrity, and actively homed to glioma tissue. Interestingly, enucleated MSCs underwent intrinsic apoptosis due to the absence of the nucleus, which subsequently triggered macrophage-specific endocytosis, thereby achieving precise delivery of CAR-plasmids to GAM. Compared with lipid nanoparticles, this strategy specifically generated sufficient numbers of CAR-M in glioma situ to achieve GBM therapy. Moreover, this process altered the immune cell profiles within the tumor by increasing cytotoxic T cells and M1-like macrophages with antitumor activity. When combined with CD47-blocking therapies, tumor growth was completely suppressed in the GBM orthotopic mouse model, resulting in a 90-d survival rate of 83%. Collectively, our strategy provides a viable platform technology for CAR-M generation in vivo, which is expected to provide an approach for GBM therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.