ArticleNature immunology2024
A second-generation M1-polarized CAR macrophage with antitumor efficacy.
Article in Nature immunology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 192 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
192 citing papers in PubMed, 2 syntheses or guidelines pooled it, 232 citations in OpenAlex.
- TIR domain proteins: regulatory mechanisms in the tumor immune microenvironment, clinical translation strategies, and prospects for precision therapy applications.Frontiers in immunology · 2025Pooled it
- Allogeneic CAR-engineered cellular therapy for relapsed and refractory large B cell lymphoma: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Preclinical advances and mechanistic insights of CAR-T therapy for acute myeloid leukemia: from target iteration to microenvironment regulation.Annals of medicine · 2026Review
- Distinct effector functions and synergy of CAR mRNA-engineered T cells and macrophages in the clearance of CD19Journal of advanced research · 2026Article
- Neutrophil-integrated syncytial CAR macrophage for cancer immunotherapy.Nature immunology · 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
- CAR design equips diverse immune cells with unique antigen-specific activation identities.Molecular therapy. Oncology · 2026Article
- Next-generation macrophage engineering in cancer therapy: From TAM reprogramming to CAR-macrophages.Molecular therapy. Nucleic acids · 2026Review
- Pathophysiological roles of monocytes and macrophages in cancer.Nature reviews. Immunology · 2026Review
- Nanomaterial Strategies for Pulmonary Delivery of Immunotherapeutics in Lung Cancer Treatment.Advanced healthcare materials · 2026Review
- Chimeric antigen receptor-macrophages: A new paradigm for cell therapy.Bioengineering & translational medicine · 2026Review
- Adoptive cell therapy in lung cancer: progress, challenges, and prospects.Chinese medical journal pulmonary and critical care medicine · 2026Review
- The M1/M2 Test System for Determining Macrophage Phenotypes.International journal of molecular sciences · 2026Review
- 25 Years of Cancer Immunoediting: Dendritic Cells and Macrophages Filled the Missing Gap.Cancers · 2026Review
- Harnessing macrophage signaling pathways and scalable engineering for next-generation immunotherapies.Signal transduction and targeted therapy · 2026Review
- Redirecting Monocyte Differentiation With Engineered Extracellular Vesicles for Glioma Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Loss of NCCRP1 overcomes immune evasion in lung adenocarcinoma.Journal for immunotherapy of cancer · 2026Article
- Cardiac immunity and heart repair: Mechanism, challenge, and future direction.Chinese medical journal · 2026Review
- CD47 monoclonal antibody enhances the inhibitory effect of anti-HER2 chimeric antigen receptor macrophages on ovarian cancer.Oncology letters · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
132 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
24 authors at 8 institutions in 3 countries.
Funding
Abstract
Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.
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What OpenQuestion holds
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.