ArticlePloS one2018
ALX148 blocks CD47 and enhances innate and adaptive antitumor immunity with a favorable safety profile.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 102 papers.
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Who cites it
102 citing papers in PubMed, 166 citations in OpenAlex.
- Phase II Clinical Trial and Preclinical Evaluation of a Novel CD47 Blockade Combination in Refractory Microsatellite-Stable Metastatic Colorectal Cancer.Cancer research communications · 2025Trial
- Evorpacept plus trastuzumab, ramucirumab and paclitaxel in HER2-positive gastric cancer: a randomized phase 2 trial.Nature medicine · 2026Article
- Mechanisms of resistance to macrophage checkpoint inhibitors in B-cell non-Hodgkin lymphoma.British journal of haematology · 2026Article
- Retargeted adenoviruses for local IgA and CD47 blocker production as a novel cancer therapy.EMBO molecular medicine · 2026Article
- DDR1 Promotes Immune Evasion in Colorectal Cancer by Orchestrating IL33-Mediated M2-like Polarization of Tumor-Associated Macrophages.Cancer immunology research · 2026Article
- Selective Targeting of Immune Checkpoints HLA-G and CD47 Using Novel Dual Signaling Protein DSP216 Promotes Innate Anticancer Immunity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting phagocytosis checkpoints for cancer immunotherapy.Nature reviews. Cancer · 2026Review
- CD47 blockade (ALX301) enhances immunoradiotherapy response in HPV negative head and neck squamous cell carcinoma.PloS one · 2026Article
- Immunogenic cell death unlocks the potential for combined radiation and immunotherapy.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Discussion on the mechanism of HER2 resistance in esophagogastric junction and gastric cancer in the era of immunotherapy.Human vaccines & immunotherapeutics · 2025Review
- Pharmacological considerations for next-generation protein therapeutics in cardiovascular disease.The Journal of pharmacology and experimental therapeutics · 2025Review
- HCB101: a novel potent ligand-trap Fc-fusion protein targeting the CD47-SIRPα pathway with high safety and preclinical efficacy for hematological and solid tumors.Journal of hematology & oncology · 2025Article
- Optimizing antibody stability and efficacy in CD47- SIRPα inhibition via computational approaches.Molecular diversity · 2025Article
- A Phase I Trial of Evorpacept, Lenalidomide, and Rituximab for Patients with B-Cell Non-Hodgkin Lymphoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Immune checkpoint molecules signal regulatory protein alpha in the development of hepatocellular carcinoma.World journal of gastrointestinal oncology · 2025Review
- Evorpacept plus rituximab for the treatment of relapsed or refractory non-Hodgkin lymphoma: results from the phase I ASPEN-01 study.Haematologica · 2025Article
- Inhibition of Extracellular Matrix Protein Fibulin-3 Reduces Immunosuppressive Signaling and Increases Macrophage Activation in Glioblastoma.Cancer research communications · 2025Article
- CD47-mediated tumor microenvironment remodeling: a central mechanism in immune evasion.Acta biochimica et biophysica Sinica · 2025Review
- Nanoparticle-formulated mRNA encoding engineered multivalent SIRPα-Fc fusion proteins shows robust anti-cancer activity in preclinical models.Molecular therapy. Nucleic acids · 2025Article
- Regulation and Function of Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): The Role of the SRIF System in Macrophage Regulation.International journal of molecular sciences · 2025Review
42 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
CD47 is a widely expressed cell surface protein that functions as an immune checkpoint in cancer. When expressed by tumor cells, CD47 can bind SIRPα on myeloid cells, leading to suppression of tumor cell phagocytosis and other innate immune functions. CD47-SIRPα signaling has also been implicated in the suppression of adaptive antitumor responses, but the relevant cellular functions have yet to be elucidated. Therapeutic blockade of the CD47 pathway may stimulate antitumor immunity and improve cancer therapy. To this end, a novel CD47-blocking molecule, ALX148, was generated by fusing a modified SIRPα D1 domain to an inactive human IgG1 Fc. ALX148 binds CD47 from multiple species with high affinity, inhibits wild type SIRPα binding, and enhances phagocytosis of tumor cells by macrophages. ALX148 has no effect on normal human blood cells in vitro or on blood cell parameters in rodent and non-human primate studies. Across several murine tumor xenograft models, ALX148 enhanced the antitumor activity of different targeted antitumor antibodies. Additionally, ALX148 enhanced the antitumor activity of multiple immunotherapeutic antibodies in syngeneic tumor models. These studies revealed that CD47 blockade with ALX148 induces multiple responses that bridge innate and adaptive immunity. ALX148 stimulates antitumor properties of innate immune cells by promoting dendritic cell activation, macrophage phagocytosis, and a shift of tumor-associated macrophages toward an inflammatory phenotype. ALX148 also stimulated the antitumor properties of adaptive immune cells, causing increased T cell effector function, pro-inflammatory cytokine production, and a reduction in the number of suppressive cells within the tumor microenvironment. Taken together, these results show that ALX148 binds and blocks CD47 with high affinity, induces a broad antitumor immune response, and has a favorable safety profile.
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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.