ArticleJournal of immunology (Baltimore, Md. : 1950)2021
Novel SIRPα Antibodies That Induce Single-Agent Phagocytosis of Tumor Cells while Preserving T Cells.
Article in Journal of immunology (Baltimore, Md. : 1950), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 41 papers.
What it found
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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.
A Phase 1/2 Multicenter, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of AO-176
A Phase 1/2, Dose Escalation Safety and Tolerability Study of AO-176 as Monotherapy and in Combination With Bortezomib and Dexamethasone in Adults With Relapsed or Refractory Multiple Myeloma
Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- Targeting Myeloid Cells for Cancer Immunotherapy.Cancer immunology research · 2025Review
- Targeting asparagine and cysteine in SARS-CoV-2 variants and human pro-inflammatory mediators to alleviate COVID-19 severity; a cross-section and in-silico study.Scientific reports · 2025Article
- Targeting the CD47-SIRPalpha checkpoint in multiple myeloma.Discover oncology · 2025Review
- 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
- HES1 in cancer: a key player in tumorigenesis and its prognostic significance.Molecular genetics and genomics : MGG · 2025Review
- CD47-Targeted Therapy in Cancer Immunotherapy: At a Crossroads of Promise and Challenge.Oncology research · 2025Review
- Deciphering the role of signal regulatory protein α in immunotherapy for solid tumors.Frontiers in immunology · 2025Review
- Sirp-α Antibody Inhibits Renal Cell Carcinoma Progression via Akt1/Akt2 Modulation in Tumor-Associated Macrophages.Journal of inflammation research · 2025Article
- A human antibody specific for SIRPα reprograms macrophages and promotes antibody mediated anti-cancer activity.PloS one · 2025Article
- Chitinase 3-like-1 Inhibits Innate Antitumor and Tissue Remodeling Immune Responses by Regulating CD47-SIRPα- and CD24-Siglec10-Mediated Phagocytosis.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Deciphering the role of CD47 in cancer immunotherapy.Journal of advanced research · 2024Review
- Next-Generation Therapies for Multiple Myeloma.Annual review of cancer biology · 2024Article
- Intracellular and extracellular synergistic therapy for restoring macrophage functions via anti-CD47 antibody-conjugated bifunctional nanoparticles in atherosclerosis.Bioactive materials · 2024Article
- Discovery and Preclinical Activity of BMS-986351, an Antibody to SIRPα That Enhances Macrophage-mediated Tumor Phagocytosis When Combined with Opsonizing Antibodies.Cancer research communications · 2024Article
- Targeting the CD47/SIRPα pathway in malignancies: recent progress, difficulties and future perspectives.Frontiers in oncology · 2024Review
- Insights into the Tumor Microenvironment-Components, Functions and Therapeutics.International journal of molecular sciences · 2023Review
- The role of CD47 in non-neoplastic diseases.Heliyon · 2023Review
- Review
- Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review.Current issues in molecular biology · 2023Review
- BYON4228 is a pan-allelic antagonistic SIRPα antibody that potentiates destruction of antibody-opsonized tumor cells and lacks binding to SIRPγ on T cells.Journal for immunotherapy of cancer · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signal regulatory protein α (SIRPα)/CD47 axis has emerged as an important innate immune checkpoint that enables cancer cell escape from macrophage phagocytosis. SIRPα expression is limited to macrophages, dendritic cells, and neutrophils-cells enriched in the tumor microenvironment. In this study, we present novel anti-SIRP Abs, SIRP-1 and SIRP-2, as an approach to targeting the SIRPα/CD47 axis. Both SIRP-1 and SIRP-2 bind human macrophage SIRPα variants 1 and 2, the most common variants in the human population. SIRP-1 and SIRP-2 are differentiated among reported anti-SIRP Abs in that they induce phagocytosis of solid and hematologic tumor cell lines by human monocyte-derived macrophages as single agents. We demonstrate that SIRP-1 and SIRP-2 disrupt SIRPα/CD47 interaction by two distinct mechanisms: SIRP-1 directly blocks SIRPα/CD47 and induces internalization of SIRPα/Ab complexes that reduce macrophage SIRPα surface levels and SIRP-2 acts via disruption of higher-order SIRPα structures on macrophages. Both SIRP-1 and SIRP-2 engage FcγRII, which is required for single-agent phagocytic activity. Although SIRP-1 and SIRP-2 bind SIRPγ with varying affinity, they show no adverse effects on T cell proliferation. Finally, both Abs also enhance phagocytosis when combined with tumor-opsonizing Abs, including a highly differentiated anti-CD47 Ab, AO-176, currently being evaluated in phase 1 clinical trials, NCT03834948 and NCT04445701 SIRP-1 and SIRP-2 are novel, differentiated SIRP Abs that induce in vitro single-agent and combination phagocytosis and show no adverse effects on T cell functionality. These data support their future development, both as single agents and in combination with other anticancer drugs.
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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.