InVivoMAb anti-mouse CD47 (IAP)

CloneCatalog #Category
MIAP301 BE0270InVivoMAb Antibodies
$150 - $3920 Login for Academic & Non-profit Pricing

About InVivoMAb anti-mouse CD47 (IAP)

The MIAP301 monoclonal antibody reacts with mouse CD47 otherwise known as integrin-associated protein (IAP). CD47 is an approximately 50 kDa glycosylated five transmembrane protein that is ubiquitously expressed by both hematopoietic cells such as T and B lymphocytes, monocytes, platelets and erythrocytes and non-hematopoietic cells. CD47 is involved in a range of cellular processes, including apoptosis, proliferation, adhesion, and migration. Furthermore, it plays a key role in immune and angiogenic responses. CD47 is a receptor for thrombospondin-1 (TSP-1), a secreted glycoprotein that plays a role in vascular development and angiogenesis. CD47 Is has been found to be overexpressed in many different tumor cells. Because of this, anti-CD47 monoclonal antibodies have been proposed and studied as a therapeutic treatment for human cancers. The MIAP301 antibody has been shown to neutralize CD47 in vivo and in vitro.

InVivoMAb anti-mouse CD47 (IAP) Specifications

Isotype Rat IgG2a, κ
Immunogen Intact CD47 purified from placenta
Reported Applications
  • in vivo CD47 blockade
  • Immunofluorescence
  • PBS, pH 7.0
  • Contains no stabilizers or preservatives
  • <2EU/mg (<0.002EU/μg)
  • Determined by LAL gel clotting assay
  • >95%
  • Determined by SDS-PAGE
Sterility 0.2 μM filtered
Production Purified from tissue culture supernatant in an animal free facility
Purification Protein G
RRID AB_2687793
Molecular Weight 150 kDa
Storage The antibody solution should be stored at the stock concentration at 4°C. Do not freeze.

Application References

InVivoMAb anti-mouse CD47 (IAP) (Clone: MIAP301)


Xu, M. M., et al. (2017). “Dendritic Cells but Not Macrophages Sense Tumor Mitochondrial DNA for Cross-priming through Signal Regulatory Protein alpha Signaling.” Immunity 47(2): 363-373 e365. PubMed

Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein alpha (SIRPalpha) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPalpha with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs. mtDNA was recognized by cyclic-GMP-AMP synthase (cGAS) in the DC cytosol, contributing to type I interferon (IFN) production and antitumor adaptive immunity. Thus, our findings have demonstrated how tumor cells inhibit innate sensing in DCs and suggested that the CD47-SIRPalpha axis is critical for DC-driven antitumor immunity.

Hsieh, C. P., et al. (2015). “Deficits in cerebellar granule cell development and social interactions in CD47 knockout mice.” Dev Neurobiol 75(5): 463-484. PubMed

CD47 is involved in neurite differentiation in cultured neurons, but the function of CD47 in brain development is largely unknown. We determined that CD47 mRNA was robustly expressed in the developing cerebellum, especially in granule cells. CD47 protein was mainly expressed in the inner layer of the external granule layer (EGL), molecular layer, and internal granule layer (IGL), where granule cells individually become postmitotic and migrate, leading to neurite fasciculation. At postnatal day 8 (P8), CD47 knockout mice exhibited an increased number of proliferating granule cells in the EGL, whereas the CD47 agonist peptide 4N1K increased the number of postmitotic cells in primary granule cells. Knocking out the CD47 gene and anti-CD47 antibody impaired the radial migration of granule cells from the EGL to the IGL individually in mice and slice cultures. In primary granule cells, knocking out CD47 reduced the number of axonal collaterals and dendritic branches; by contrast, overexpressing CD47 or 4N1K treatment increased the axonal length and numbers of axonal collaterals and dendritic branches. Furthermore, the length of the fissure between Lobules VI and VII was decreased in CD47 knockout mice at P21 and at 14 wk after birth. Lastly, CD47 knockout mice exhibited increased social interaction at P21 and depressive-like behaviors at 10 wk after birth. Our study revealed that the cell adhesion molecule CD47 participates in multiple phases of granule cell development, including proliferation, migration, and neurite differentiation implying that aberrations of CD47 are risk factors that cause abnormalities in cerebellar development and atypical behaviors.

Liu, X., et al. (2015). “CD47 blockade triggers T cell-mediated destruction of immunogenic tumors.” Nat Med 21(10): 1209-1215. PubMed

Macrophage phagocytosis of tumor cells mediated by CD47-specific blocking antibodies has been proposed to be the major effector mechanism in xenograft models. Here, using syngeneic immunocompetent mouse tumor models, we reveal that the therapeutic effects of CD47 blockade depend on dendritic cell but not macrophage cross-priming of T cell responses. The therapeutic effects of anti-CD47 antibody therapy were abrogated in T cell-deficient mice. In addition, the antitumor effects of CD47 blockade required expression of the cytosolic DNA sensor STING, but neither MyD88 nor TRIF, in CD11c(+) cells, suggesting that cytosolic sensing of DNA from tumor cells is enhanced by anti-CD47 treatment, further bridging the innate and adaptive responses. Notably, the timing of administration of standard chemotherapy markedly impacted the induction of antitumor T cell responses by CD47 blockade. Together, our findings indicate that CD47 blockade drives T cell-mediated elimination of immunogenic tumors.

Maute, R. L., et al. (2015). “Engineering high-affinity PD-1 variants for optimized immunotherapy and immuno-PET imaging.” Proc Natl Acad Sci U S A 112(47): E6506-6514. PubMed

Signaling through the immune checkpoint programmed cell death protein-1 (PD-1) enables tumor progression by dampening antitumor immune responses. Therapeutic blockade of the signaling axis between PD-1 and its ligand programmed cell death ligand-1 (PD-L1) with monoclonal antibodies has shown remarkable clinical success in the treatment of cancer. However, antibodies have inherent limitations that can curtail their efficacy in this setting, including poor tissue/tumor penetrance and detrimental Fc-effector functions that deplete immune cells. To determine if PD-1:PD-L1-directed immunotherapy could be improved with smaller, nonantibody therapeutics, we used directed evolution by yeast-surface display to engineer the PD-1 ectodomain as a high-affinity (110 pM) competitive antagonist of PD-L1. In contrast to anti-PD-L1 monoclonal antibodies, high-affinity PD-1 demonstrated superior tumor penetration without inducing depletion of peripheral effector T cells. Consistent with these advantages, in syngeneic CT26 tumor models, high-affinity PD-1 was effective in treating both small (50 mm(3)) and large tumors (150 mm(3)), whereas the activity of anti-PD-L1 antibodies was completely abrogated against large tumors. Furthermore, we found that high-affinity PD-1 could be radiolabeled and applied as a PET imaging tracer to efficiently distinguish between PD-L1-positive and PD-L1-negative tumors in living mice, providing an alternative to invasive biopsy and histological analysis. These results thus highlight the favorable pharmacology of small, nonantibody therapeutics for enhanced cancer immunotherapy and immune diagnostics.

Shi, L., et al. (2015). “CD47 deficiency ameliorates autoimmune nephritis in Fas(lpr) mice by suppressing IgG autoantibody production.” J Pathol 237(3): 285-295. PubMed

CD47, a self-recognition marker, plays an important role in both innate and adaptive immune responses. To explore the potential role of CD47 in activation of autoreactive T and B cells and the production of autoantibodies in autoimmune disease, especially systemic lupus erythematosus (SLE), we have generated CD47 knockout Fas(lpr) (CD47(-/-) -Fas(lpr) ) mice and examined histopathological changes in the kidneys, cumulative survival rates, proteinuria, extent of splenomegaly and autoantibodies, serum chemistry and immunological parameters. In comparison with Fas(lpr) mice, CD47(-/-) -Fas(lpr) mice exhibit a prolonged lifespan and delayed autoimmune nephritis, including glomerular cell proliferation, basement membrane thickening, acute tubular atrophy and vacuolization. CD47(-/-) -Fas(lpr) mice have lower levels of proteinuria, associated with reduced deposition of complement C3 and C1q, and IgG but not IgM in the glomeruli, compared to age-matched Fas(lpr) mice. Serum levels of antinuclear antibodies and anti-double-stranded DNA antibodies are significantly lower in CD47(-/-) -Fas(lpr) than in Fas(lpr) mice. CD47(-/-) -Fas(lpr) mice also display less pronounced splenomegaly than Fas(lpr) mice. The mechanistic studies further suggest that CD47 deficiency impairs the antigenic challenge-induced production of IgG but not IgM, and that this effect is associated with reduction of T follicular cells and impairment of germinal centre development in lymphoid tissues. In conclusion, our results demonstrate that CD47 deficiency ameliorates lupus nephritis in Fas(lpr) mice via suppression of IgG autoantibody production. Copyright (c) 2015 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Vermeer, D. W., et al. (2013). “Radiation-induced loss of cell surface CD47 enhances immune-mediated clearance of human papillomavirus-positive cancer.” Int J Cancer 133(1): 120-129. PubMed

The increasing incidence of human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OSSC) demands development of novel therapies. Despite presenting at a more advanced stage, HPV(+) oropharyngeal squamous cell carcinoma (OSCC) have a better prognosis than their HPV(-) counterparts. We have previously demonstrated that clearance of HPV(+) OSCC during treatment with radiation and chemotherapy requires an immune response which is likely responsible for the improved clinical outcomes. To further elucidate the mechanism of immune-mediated clearance, we asked whether radiation therapy induces tumor cell changes that allow the body to recognize and aid in tumor clearance. Here, we describe a radiation-induced change in tumor surface protein expression that is critical for immune-mediated clearance. Radiation therapy decreases surface expression of CD47, a self-marker. CD47 is frequently overexpressed in head and neck squamous cell carcinoma and radiation induces a decrease of CD47 in a dose-dependent manner. We show that both in vitro and in vivo tumor cell CD47 protein levels are restored over time after sublethal radiation exposure and that protein levels on adjacent, normal tissues remain unaffected. Furthermore, reduction of tumor cell CD47 increases phagocytosis of these cells by dendritic cells and leads to increased interferon gamma and granzyme production from mixed lymphocytes. Finally, decreasing tumor cell CD47 in combination with standard radiation and chemotherapy results in improved immune-mediated tumor clearance in vivo. These findings help define an important mechanism of radiation-related immune clearance and suggest that decreasing CD47 specifically on tumor cells may be a good therapeutic target for HPV related disease.

Majeti, R., et al. (2009). “CD47 is an adverse prognostic factor and therapeutic antibody target on human acute myeloid leukemia stem cells.” Cell 138(2): 286-299. PubMed

Acute myeloid leukemia (AML) is organized as a cellular hierarchy initiated and maintained by a subset of self-renewing leukemia stem cells (LSC). We hypothesized that increased CD47 expression on human AML LSC contributes to pathogenesis by inhibiting their phagocytosis through the interaction of CD47 with an inhibitory receptor on phagocytes. We found that CD47 was more highly expressed on AML LSC than their normal counterparts, and that increased CD47 expression predicted worse overall survival in three independent cohorts of adult AML patients. Furthermore, blocking monoclonal antibodies directed against CD47 preferentially enabled phagocytosis of AML LSC and inhibited their engraftment in vivo. Finally, treatment of human AML LSC-engrafted mice with anti-CD47 antibody depleted AML and targeted AML LSC. In summary, increased CD47 expression is an independent, poor prognostic factor that can be targeted on human AML stem cells with blocking monoclonal antibodies capable of enabling phagocytosis of LSC.

Chang, H. P., et al. (2001). “Functional blocking of integrin-associated protein impairs memory retention and decreases glutamate release from the hippocampus.” Neuroscience 102(2): 289-296. PubMed

We have previously demonstrated that integrin-associated protein is involved in memory consolidation of one-way inhibitory avoidance learning in rats and mice. In the present study, we examined the effects of functional blocking of integrin-associated protein on memory retention, long-term potentiation and glutamate release in mice as well as on cell attachment to extracellular matrix protein in primary cultures. The results indicated that integrin-associated protein monoclonal antibody miap301, when directly injected into the dentate gyrus of the hippocampus at moderate doses, significantly impairs memory retention in mice in the same one-way inhibitory avoidance task and decreases the amplitude of tetanic stimulation-induced long-term potentiation in dentate gyrus neurons. At a dose that effectively impairs both memory retention and long-term potentiation, integrin-associated protein monoclonal antibody also significantly blocks potassium chloride-induced glutamate release from the hippocampus in vivo. Results from western blot confirmed the presence of integrin-associated protein at the synaptic area. Cell adhesion experiments further revealed that integrin-associated protein monoclonal antibody markedly inhibits granular cell attachment to thrombospondin, the extracellular matrix protein known to bind integrin-associated protein, but not to collagen and laminin, the extracellular matrix proteins known to bind integrin. From these results we suggest that integrin-associated protein monoclonal antibody may impair synaptic plasticity and behavioral plasticity in mice through blockade of granular cell attachment to extracellular matrix protein and the subsequent signal transduction, and through inhibition of glutamate release from the hippocampus.