CD47 monoclonal antibody

BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) is an important cause of early dysfunction and exacerbation of immune rejection in transplanted hearts. The integrin-related protein CD47 exacerbates myocardial ischemia-reperfusion injury by inhibiting the nitric oxide signaling pathway through interaction with thrombospondin-1 (TSP-1). In addition, the preservation quality of the donor hearts is a key determinant of transplant success. Preservation duration beyond four hours is associated with primary graft dysfunction...

Antibody-based CD47 blockade aims to activate macrophage phagocytosis of tumor cells. However, macrophages possess a high degree of phenotype heterogeneity that likely influences phagocytic capacity. In murine models, proinflammatory (M1) activation increases macrophage phagocytosis of tumor cells, but in human models, results have been conflicting. Here, we investigated the effects of proinflammatory polarization on the phagocytic response of human monocyte-derived macrophages in an in vitro model. Using both flow cytometry-based and fluorescence live-cell imaging-based phagocytosis assays, we observed that mouse monoclonal anti-CD47 antibody (B6H12) induced monocyte-derived macrophage phagocytosis of cancer cells in vitro...

Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma...

CD47-SIRPα axis is an immunotherapeutic target in tumor therapy. However, current monoclonal antibody targeting CD47-SIRPα axis is associated with on-target off-tumor and antigen sink effects, which significantly limit its potential clinical application. Herein, a biomimetic nano-degrader is developed to inhibit CD47-SIRPα axis in a site-specific manner through SIRPα degradation, and its efficacy in acute myocardial infarction (AMI) is evaluated. The nano-degrader is constructed by hybridizing liposome with red blood cell (RBC) membrane (RLP), which mimics the CD47 density of senescent RBCs and possesses a natural high-affinity binding capability to SIRPα on macrophages without signaling capacity...

BACKGROUND: Targeting CD47/SIRPα axis has emerged as a promising strategy in cancer immunotherapy. Despite the encouraging clinical efficacy observed in hematologic malignancies through CD47-SIRPα blockade, there are safety concerns related to the binding of anti-CD47 antibodies to CD47 on the membrane of peripheral blood cells. METHODS: In order to enhance the selectivity and therapeutic efficacy of the antibody, we developed a humanized anti-CD47 monoclonal antibody called Gentulizumab (GenSci059)...

INTRODUCTION: Immune checkpoint inhibitors have achieved great success in treatment of many different types of cancer. Programmed cell death protein ligand 1 (PD-L1, CD274) is a major immunosuppressive immune checkpoint and a target for several already approved monoclonal antibodies. Despite this, novel strategies are under development, as the overall response remains low. AREAS COVERED: In this review, an overview of the current biomarkers for response to PD-L1 inhibitor treatment is given, followed by a discussion of potential novel biomarkers, including tumor mutational burden and circulating tumor DNA...

Cluster of differentiation 47 (CD47) is a transmembrane protein highly expressed in tumor cells that interacts with signal regulatory protein alpha (SIRPα) and triggers a "don't eat me" signal to the macrophage, inhibiting phagocytosis and enabling tumor escape from immunosurveillance. The CD47-SIRPα axis has become an important target for cancer immunotherapy. To date, the advancement of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hematologic toxicity including anemia...

In normal cells, binding of the transmembrane protein CD47 to signal regulatory protein-α (SIRPα) on macrophages induces an anti-phagocytic signal. Tumor cells hijack this pathway and overexpress CD47 to evade immune destruction. Macrophage antitumor activity can be restored by simultaneously blocking the CD47-SIRPα signaling axis and inducing a pro-phagocytic signal via tumor opsonizing antibodies. We identified a novel, fully human monoclonal antibody (BMS-986351) that binds SIRPα with high affinity...

PURPOSE: Develop a novel therapeutic strategy for patients with subtypes of mature T-cell and NK-cell neoplasms. EXPERIMENTAL DESIGN: Primary specimens, cell lines, patient-derived xenograft models, commercially available and proprietary anti-KLRG1 antibodies were used for screening, target, and functional validation. RESULTS: Here we demonstrate that surface KLRG1 is highly expressed on tumor cells in subsets of patients with extranodal NK/T-cell lymphoma (ENKTCL), T-prolymphocytic leukemia (T-PLL) and gamma/delta T-cell lymphoma (G/D TCL)...

CD47 acts as a defense mechanism for tumor cells by sending a "don't eat me" signal via its bond with SIRPα. With CD47's overexpression linked to poor cancer outcomes, its pathway has become a target in cancer immunotherapy. Though monoclonal antibodies offer specificity, they have limitations like the large size and production costs. Nanobodies, due to their small size and unique properties, present a promising therapeutic alternative. In our study, a high-affinity anti-CD47 nanobody was engineered from an immunized alpaca...

Exosomes are proposed to be important in the pathogenesis of prevalent neurodegenerative diseases. We report the first application of solid-state technology to perform multiplex analysis of single exosomes in human cerebrospinal fluid (CSF) obtained from the lumbar sac of people diagnosed with Alzheimer's disease dementia (ADD, n=30) or Parkinson's disease dementia (PDD, n=30), as well as age-matched health controls (HCN, n=30). Single events were captured with mouse monoclonal antibodies to one of three different tetraspanins (CD9, CD63, or CD81) or with mouse (M) IgG control, and then probed with fluorescently labeled antibodies to prion protein (PrP) or CD47 to mark neuronal or presynaptic origin, as well as ADD- and PDD-related proteins: amyloid beta (Aβ), tau, α-synuclein, and Apolipoprotein (Apo) E...

Since the successful introduction of checkpoint inhibitors targeting the adaptive immune system, monoclonal antibodies inhibiting CD47-SIRPα interaction have shown promise in enhancing anti-tumor treatment efficacy. Apart from SIRPα, neutrophils express a broad repertoire of inhibitory receptors, including several members of the sialic acid-binding receptor (SIGLEC) family. Here, we demonstrate that interaction between tumor cell-expressed sialic acids and SIGLEC-5/14 on neutrophils inhibits antibody-dependent cellular cytotoxicity (ADCC)...

Dual targeting to immune checkpoints has achieved a better therapeutic efficacy than single targeting due to synergistic extrication of tumour immunity. However, most dual targeting strategies are usually antibody dependent which facing drawbacks of antibodies, such as poor solid tumour penetration and unsatisfied affinity. To meet the challenges, we engineered a cell membrane displaying a fusion protein composed of SIRPα and PD-1 variants, the high-affinity consensus (HAC) of wild-type molecules, and with which prepared nanovesicles (NVs)...

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Checkpoint inhibitor therapy has emerged as an effective therapeutic strategy for many types of malignancies, especially in solid tumors. Within the last two decades, numerous monoclonal antibody drugs targeting the CTLA-4 and PD-1/PD-L1 checkpoint pathways have seen FDA approval. Within hematologic malignancies, Hodgkin Lymphoma has seen the greatest clinical benefits thus far with more recent data showing efficacy in the front-line setting. As our understanding of checkpoint inhibition expands, using these pathways as a therapeutic target has shown some utility in the treatment of other hematologic malignancies as well, primarily in the relapsed/refractory settings...

BACKGROUND: Anti-CD47 monoclonal antibodies have increasing clinical applications in the treatment of cancer. However, anti-CD47 monoclonal antibodies interfere with immunohematology testing in patients who require blood transfusion. As the current approaches to removing any interferences have technical problems, new methods need to be developed to resolve anti-CD47 interference in immunohematology testing. MATERIALS AND METHODS: We evaluated the Daudi cell line for the adsorption of free anti-CD47 monoclonal antibodies from patients' plasma to facilitate immunohematology testing in patients treated with anti-CD47 monoclonal antibody...

Numerous recent advances have been made in therapeutic approaches toward acute myeloid leukemia (AML). Since 2017, we have seen eleven novel Food & Drug Administration (FDA)-approved medications for AML, all of which extend beyond the classical cytarabine-based cytostatic chemotherapy. In the recent two decades, the role of immune surveillance in AML has been intensively investigated. The power of one's own innate and adaptive immunity has been harnessed pharmacologically toward the goal of clearance of AML cells...

Phagocytic elimination of solid tumors by innate immune cells seems attractive for immunotherapy, particularly because of the possibilities for acquired immunity. However, the approach remains challenging, with blockade of the macrophage checkpoint CD47 working in immunodeficient mice and against highly immunogenic tumors but not in the clinic where tumors are poorly immunogenic. Even when mouse tumors of poorly immunogenic B16F10 melanoma are opsonized to drive engulfment with a suitable monoclonal antibody (mAb), anti-CD47 blockade remains insufficient...

Macrophages are essential mediators of innate immunity. Non-self-cells resist phagocytosis through the expression of the checkpoint molecule CD47. CD47, as the integrin-associated protein, is overexpressed on tumor and SARS-CoV-2-infected cells as a potential surface biomarker for immune surveillance evasion. CD47-signal-regulating protein alpha (SIRPα) interaction is a promising innate immunotarget. Previous findings based on monoclonal antibodies (mAbs) or fusion proteins that block CD47 or SIRPα have been developed in cancer research...

CD47/SIRPα pathway is a new breakthrough in the field of tumor immunity after PD-1/PD-L1. While current monoclonal antibody therapies targeting CD47/SIRPα have demonstrated some anti-tumor effectiveness, there are several inherent limitations associated with these formulations. In the paper, we developed a predictive model that combines next-generation phage display (NGPD) and traditional machine learning methods to distinguish CD47 binding peptides. First, we utilized NGPD biopanning technology to screen CD47 binding peptides...