What is anti-CD47?
Anti-CD47 antibodies enhance the phagocytosis of tumor cells by macrophages by directly blocking the binding of tumor cell-expressing CD47 to macrophage-expressing SIRPα (18).
What is Hu5F9 G4?
The Hu5F9-G4 (hereafter, 5F9) antibody is a macrophage immune checkpoint inhibitor blocking CD47 that induces tumor-cell phagocytosis. 5F9 synergizes with rituximab to eliminate B-cell non-Hodgkin’s lymphoma cells by enhancing macrophage-mediated antibody-dependent cellular phagocytosis.
Is chemo a Magrolimab?
Magrolimab is an investigational, potential first-in-class, anti-CD47 monoclonal antibody being studied in previously untreated acute myeloid leukemia (AML) patients who are ineligible for intensive chemotherapy, including patients with TP53-mutant AML.
How is Magrolimab given?
Magrolimab or placebo is administered intravenously (IV) with an initial 1 mg/kg priming dose to mitigate on target anemia. An intrapatient dose escalation regimen up to 30 mg/kg is then administered through Cycle 1, 30 mg/kg weekly dosing in Cycle 2, with 30 mg/kg Q2W dosing occurring in Cycle 3 and beyond.
Who discovered CD47?
Concurrently, Eric Brown had discovered CD47 2 and suggested that it might be the TSP1 receptor. We confirmed that the 50 kDa protein was recognized by several CD47 antibodies and that the TSP1 G domain peptides augmented integrin functions such as chemotaxis and cell spreading in a CD47-dependent manner 5, 26.
Where is CD47 found?
CD47 is a kind of protein that is found on the surface of many cells in the body. It tells circulating immune cells called macrophages not to eat these cells. The body uses the CD47 protein to protect cells that should be protected and to help dispose of cells that are aged or diseased.
What is Magrolimab?
A humanized monoclonal antibody targeting the human cell surface antigen CD47, with potential immunostimulating and antineoplastic activities.
What are the side effects of azacitidine?
Azacitidine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:
- nausea.
- vomiting.
- diarrhea.
- constipation.
- sores on the mouth or tongue.
- hemorrhoids.
- stomach pain or tenderness.
- heartburn.
Is Venclexta approved for MDS?
“We are pleased that the FDA has granted Venclexta its sixth Breakthrough Therapy Designation in recognition of its potential to improve outcomes for people with MDS in combination with azacitidine.”
What is high risk MDS?
Higher-risk myelodysplastic syndromes (MDS) are defined by patients who fall into higher-risk group categories in the original or revised International Prognostic Scoring System. Survival for these patients is dismal, and treatment should be initiated rapidly.
How do I block CD47?
To block erythrocyte CD47, anti-CD47 B6H12 monoclonal antibody was used. The B6H12 antibody blocks the interaction between CD47 and SIRP-α. IgG was used as a control. The dose of 10 or 20 µg/mL has been found to enhance phagocytosis of tumor cells.
Where does protein CD47 come from?
CD47 is an integral membrane protein consisting of an N-terminal extracellular IgV domain derived from the immunoglobulin superfamily followed by a presenilin domain containing five membrane-spanning segments and ending in a short variably spliced cytoplasmic sequence (Fig.
Are there any clinical trials for anti CD47?
The anti-CD47 cancer therapy clinical trials. The clinical trials of the anti-CD47 antibody are underway. As with most FDA phase-1 safety trials, the clinical trial is small and is not currently recruiting additional patients.
What does CD47 do to a cancer cell?
Researchers at Stanford have discovered that nearly every kind of cancer cell has a large amount of CD47 on the cell surface. This protein signal protects the cancer against attack by the body’s immune system.
Is there a maximum tolerated dose of CD47?
No maximum tolerated dose was reached with maintenance doses up to 45 mg/kg. At doses of 10 mg/kg or more, the CD47 antigen sink was saturated by 5F9, and a 5F9 half-life of approximately 13 days was observed. Strong antibody staining of tumor tissue was observed in a patient at 30 mg/kg.
How does a monoclonal antibody against CD47 work?
(Right) A blocking monoclonal antibody directed against CD47 disrupts the dominant inhibitory SIRP signal in phagocytes, which unmasks the pro-phagocytic stimulus on cancer cells resulting in their phagocytic elimination. Normal cells lack pro-phagocytic stimuli, and thus are unaffected by the blocking anti-CD47 antibody.