CD47 Antibodies

Leukocyte surface antigen CD47 (CD47)

Has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. Plays an essential role in memory formation and synaptic plasticity in the hippocampus (By similarity).

Receptor for SIRPA, binding to that prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cell-cell adhesion, enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation.

Gene Information

Human
Gene Name:	CD47
Uniprot:	Q08722
Entrez:	961

Family

Belongs to:
No superfamily

Alternative Names

antigen identified by monoclonal 1D8; Antigenic surface determinant protein OA3; CD47 antigen (Rh-related antigen, integrin-associated signal transducer); CD47 antigen; CD47 glycoprotein; CD47 molecule; CD47; IAP; IAPintegrin associated protein; Integrin-associated protein; leukocyte surface antigen CD47; MER6integrin-associated signal transducer; OA3; Protein MER6; Rh-related antigen

Molecular Weight

Mass (kDA):
35.214 kDA

Genomic Context

Human
Location:	3q13.12
Sequence:	3; NC_000003.12 (108043094..108094200, complement)

Subcellular Localizations

Cell membrane; Multi-pass membrane protein.

Diseases

• Tissue Adhesions
• Neoplasms
• Inflammation
• Malignant Neoplasms
• Leukemia
• Autoimmune Reaction
• Pertussis
• Anemia
• Anemia, Hemolytic
• Nervousness
• Ischemia
• Tumor Angiogenesis
• Autoimmune Diseases

• Inflammatory Response
• Carcinoma
• Melanoma
• Neoplasm Metastasis
• Hemolysis (disorder)
• Autoimmune Hemolytic Anemia
• Leukemia, Myelocytic, Acute

Interacting Proteins

• SIRPG
• SYNE4

Pathways

• Phagocytosis
• Cell Adhesion
• Cell Death
• Secretion
• Cell Migration
• Chemotaxis
• Pathogenesis
• Cell Activation
• Cell Proliferation
• Angiogenesis
• Inflammatory Response
• Immune Response
• Platelet Aggregation

• Transport
• Aging
• T Cell Activation
• Localization
• Glycosylation
• Cytokine Production
• Platelet Activation

PTMs

• Phosphorylation
• Glycosylation
• Cleavage
• Dephosphorylation

• Biotinylation
• Reduction
• Deglycosylation
• Oxidation

• Myristoylation

Research Areas

• Immunology
• Signal Transduction

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/CD47

Best Uses of the CD47 Marker

Tumor initiating cells also known as cancer stem cell cells express the CD47 Marker. They self-renew and maintain the mass of tumors. They play an important part in the development in the progression, relapse, and metastasis stages of cancer. CD47 is a ligand of signal-regulatory protein A and blocks phagocytosis. In lung cancer, CD47 expression is found on cancerous cells.

Anti-CD47 antibody

Lung cancer is a significant target for anti-CD47 antibodies. This specific antigen is found to be overexpressed on cancerous lung cells, including the cancer stem cells (CSCs). Patients with lung cancer have a lower rate of survival when CD47 and CD133 mRNAs are expressed. Anti-CD47 antibodies enable macrophages to phagocytose cells from lung cancer. Anti-CD47 antibodies slow the growth of lung cancer cells in immunodeficient mice and CSCs in CSC-deficient mice. They also improve survival rates in tumor-bearing animals.

Beijing Biocytogen Co., Ltd., Beijing, China carried out a clinical trial using the anti CD47 antibody with a double knock in model to assess its anti-tumor activity. During the study, mice were given 10 mg of anti-CD47 antibodies on days 0 2, 3, and 4. For analysis of blood chemistry the serum was prepared on days 6 13, 13 and 20. On day 13, whole blood was analysed to determine the complete blood count and morphology of cells.

In addition to blocking tumor growth and metastasis, this antibody also has anti-tumor properties. It blocks the "don’t-eat-mesignal that is present on the surface of cancer cells and causes macrophages and other cells to ingest the cancer cells. Although this anti-CD47 antibody has not yet been tested on humans, preliminary findings suggest that it could help reduce the incidence of human cancers in animal models. The anti-CD47 antibody is in clinical trials at Oxford University.

The anti-CD47 monoclonal antibody has been tested on mice with normal blood cell counts. The antibody was administered to normal C57BL/6 mice, and was monitored for 28 days. A complete blood count showed the decrease in white blood cells as well as red blood cells, but there was no decrease in hemoglobin. The study did not cause thrombocytopenia. These results are positive. However toxic tests are required before this antibody can be approved for human use.

The anti-CD47 antibody produced by BosterBio has been shown to slow lung cancer growth after being tested in a mouse model. It has also been examined in A549 engrafted cell lines. In this study, anti-CD47 antibody decreased tumor burden and prolonged survival in NOD/SCID mice. The study also demonstrated that the antibody can target human SIRPa which is a crucial cancer suppressor.

Functions

Despite its widely-publicized role in the immune system, scientists are still uncertain about the precise functions of the CD47 marker. The markers are involved in many pathophysiological processes, including neutrophil chemotaxis as well as the development of the nervous system. It also plays an important regulatory role in immune tolerance and T-cell activation. This article outlines some of the most important roles of the CD47 marker. This article also discusses some of the most intriguing roles of the CD47 marker.

CD47's primary purpose is to stimulate phagocyte activity against cancer cells. Another purpose is to stimulate tumor-specific immune cells. Tumor evasion is possible by the CD47-SIRPa connection. A variety of biological agents have been investigated in clinical trials to focus on this interaction. They are able to alter the an innate immune response as well as target cancer-related genes. In addition, several molecules that target the CD47-SIRPa interplay have synergistic effects.

The CD47 marker binds to TSP-1, a calcium-binding proteins that is a major component of platelet Agranules. It is released from platelet a granules when the cell is activated. This protein is involved in several biological processes such as inflammation, immune responses, adhesion migration, thrombus creation, and homeostasis.

In addition to its function in the microenvironment, CD47 also regulates the expression of Cdc42, a protein involved in the invasion phenotype that is characteristic of NSCLC cells. Blocking the expression of Cdc42 or CD47 can prevent metastasis of NSCLC cells. The CD47 marker is vital for a variety of immune system processes.

Patients with FL and DLBCL tumors experience durable and tolerable complete responses when treated with the anti-CD47 antibody Hu5F9–G4. (HU5F9). It also stimulates phagocytic cell phagocytic stroma attack cancerous cells. Rituxima antibody increased this effect. The results suggest that targeting CD47 with rituxima-specific antibodies is a possible method for immunotherapy against cancer.

A recent study revealed that CD47 was elevated in BALL and PEL cells, and therapeutic knockdown of the protein led to phagocytosis of lymphoma cells. It also inhibited the invasion of organs and ascites growth in a mouse xenograft model. Finally, in addition to anti-CD47 antibody therapy, patients with B-ALL also had increased levels of CD47.

Clinical applications

The CD47 marker is a transmembrane protein that is located on the surface of all human tumor cells. It is recognized as a ligand for the SIRPa protein, which is expressed on dendritic cells as well as macrophages. CD47 is a ligand for SIRPa and instigates an anti-tumor reaction. This signal is also referred to as the "don’t consume me" signal.

Numerous studies have demonstrated that CD47 is very abundant in xenograft samples. The expression of CD47 on normal cells was also highly compatible with the findings. While it has yet to be demonstrated that CD47 can predict survival It has been demonstrated to have potential therapeutic value. This marker can be used as a stand-alone marker or in conjunction with other drugs for treatment of hematological neoplasms. This research has shown that CD47 can be targeted to stop tumor growth and metastatic spread in different histological malignancies.

CD47 is not directly associated with cancer but it is connected with various risk factors. Tumors associated with macrophages are required for the growth and metastasis of solid tumors. Transfused cells are protected from macrophages by a surface marker called CD47. CD47-expressing hematopoietic stem cell expression increases their expression when passing through the sinusoids. If they are relocating to marrow niches, CD47 expression levels decrease. The expression of CD47 can indicate phagocytosis.

Stanford University researchers used large number of colorectal tumor samples to evaluate its anti-CD47 capability. They utilized Maxstat to measure CD47 expression by defining tumors, and surrounding normal tissue, using a higher CD47 group. After estimating median absolute CD47 antibody binding, the researchers calculated log-rank P values. Moreover, they used Affymetrix arrays to normalize raw CEL files.

Besides being a cancer biomarker, CD47 regulates innate immunity. In excess, the expression of CD47 allows for the evasion of immune surveillance. PD-L1 is a protein that is typically expressed on antigen-presenting cell lines and it is expressed in pathologically different forms of cancer. It inhibits T-cell-mediated immunity through its interaction with the programmed cell death-1 receptor (PD-1). Boussiotis reviewed the PD-1/PD-1 axis in detail in the latest studies.

Safety

A growing body of evidence suggests the CD47 marker can be used to identify tumor cells. It is an a cell surface glycoprotein with a 50kD that belongs to the immunoglobulin group. It is present on almost all cells in the body and plays an essential function in the autoimmunity process and in immune responses. It functions as a signaling protein and transmits a "don’t me eat me" message to block the process of phagocytosis. Patients with certain types of cancers of the blood have had less favorable clinical outcomes when CD47 is expressed.

There are no current treatments for cancer that rely on the CD47 marker. However, the research is promising. Aloxila, is a drug that targets CD47 and boosts innate and adaptive immune responses it is a promising treatment for advanced cancers of the hematologic spectrum. Its safety profile is positive, since it boosts the immune system against tumors. But more studies are needed to determine if the latest medications can improve outcomes for patients.

It was initially identified to interact directly with the avb3integrins. However it has been demonstrated to interact with a variety of other integrins. A2b1 has a role in the process of smooth muscle cell migration A4b1 is involved with the adhesion of reticulocytes, A5b1 plays a role in adhesion of chondrocytes and a6b1 is involved in the activation of microglia by fibrillar b-amyloid and the process of phagocytosis.

Biochemical agents that target the CD47-SIRPa interaction have been studied as possible cancer treatment options. They enhance the efficiency and activity of phagocytes when fighting tumor cells by targeting the immune system's innate defenses. These drugs can be combined to generate synergistic results. Clinical trials have also demonstrated promise for biological agents that target CD47SIRPa. It's not yet clear if these drugs will be safe and effective for patients suffering from various types of hematological malignancies.

These results are encouraging, but more research is required to determine the effects of anti CD47 drugs on patients. There are currently several treatments that inhibit the activity CD47 in cancer. TSP1 and anthracyclines are two of the choices. This therapy stops the development of breast cancer that is invasive and reduces cardiac toxicities. Both anti-CD47 treatments have an effect on autophagy.