ArticleCellular & molecular immunology2024
Silencing of SIRPα enhances the antitumor efficacy of CAR-M in solid tumors.
Article in Cellular & molecular immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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The trial behind it
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
49 citing papers in PubMed.
- Distinct effector functions and synergy of CAR mRNA-engineered T cells and macrophages in the clearance of CD19Journal of advanced research · 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
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Aurora A exacerbates antibiotic-resistant Staphylococcus aureus infection through ASC phosphorylation.EMBO reports · 2026Article
- Tissue-Resident Macrophage in Inflammation and Cancer.MedComm · 2026Review
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- 25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap.Cancers · 2026Review
- Delivering the future of immunotherapy: A state-of-the-art review of gene editing in immune cells with lipid nanoparticles.Materials today. Bio · 2026Review
- Targeting the CD47-SIRPα phagocytic checkpoint in cancer: Biology, translational opportunities, and next-generation therapeutic strategies.Smart molecules : open access · 2026Review
- Review
- SIRPα ablated iPSC-derived macrophages resist hypophagia and enhance mAb-dependent and CAR-mediated cytotoxicity of solid tumors.Molecular therapy. Oncology · 2026Article
- An in situ generated CAR-M with IFN-γ and negative dominance Sirpα isoform augments hepatocellular carcinoma immunotherapy.Journal of nanobiotechnology · 2026Article
- Targeting NK cell CLEC12B enhances cancer immunotherapy.Nature immunology · 2026Article
- Article
- Optimizing next-generation CAR-macrophages against solid tumors: challenges and potential strategies.Journal of hematology & oncology · 2026Review
- 3D-printed implantable CAR-macrophages for post-surgery cancer immunotherapy.Journal of nanobiotechnology · 2026Article
- Review
- Engineering macrophages for cancer immunotherapy: emerging insights and therapeutic potential.npj biomedical innovations · 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
Corrections and comments
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Authors and funding
13 authors.
Funding
Abstract
The potential of macrophage-mediated phagocytosis as a cancer treatment is promising. Blocking the CD47-SIRPα interaction with a CD47-specific antibody significantly enhances macrophage phagocytosis. However, concerns regarding their toxicity to nontumor cells remain substantial. Here, we engineered chimeric antigen receptor macrophages (CAR-Ms) by fusing a humanized single-chain variable fragment with FcγRIIa and integrating short hairpin RNA to silence SIRPα, thereby disrupting the CD47-SIRPα signaling pathway. These modified CAR-shSIRPα-M cells exhibited an M1-like phenotype, superior phagocytic function, substantial cytotoxic effects on HER2-positive tumor cells, and the ability to eliminate patient-derived organoids. In vivo, CAR-M cells significantly inhibited tumor growth and prolonged survival in tumor-bearing mice. Notably, CAR-shSIRPα-M cells enhanced cytotoxic T-cell infiltration into tumors, thereby enhancing the antitumor response in both the humanized immune system mouse model and immunocompetent mice. Mechanistically, SIRPα inhibition activated inflammatory pathways and the cGAS-STING signaling cascade in CAR-M cells, leading to increased production of proinflammatory cytokines, reactive oxygen species, and nitric oxide, thereby enhancing their antitumor effects. These findings underscore the potential of SIRPα inhibition as a novel strategy to increase the antitumor efficacy of CAR-M cells in cancer immunotherapy, particularly against solid tumors.
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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.