336 results about "CD47" patented technology

Methods are provided to manipulate phagocytosis of cancer cells, including e.g. leukemias, solid tumors including carcinomas, etc.

Methods are provided for treatment of hematologic cancers, particularly lymphomas and leukemias, including without limitation myelogenous and lymphocytic leukemias. A combination of antibodies specific for CD47; and specific for a cancer associated cell surface marker are administered to the patient, and provide for a synergistic decrease in cancer cell burden. The combination of antibodies may comprise a plurality of monospecific antibodies, or a bispecific or multispecific antibody. Markers of interest include without limitation, CD20, CD22, CD52, CD33; CD96; CD44; CD123; CD97; CD99; PTHR2; and HAVCR2.

Provided herein are compositions and methods for preventing, ameliorating, and / or reducing tissue ischemia and / or tissue damage due to ischemia, increasing blood vessel diameter, blood flow and tissue perfusion in the presence of vascular disease including peripheral vascular disease, atherosclerotic vascular disease, coronary artery disease, stroke and influencing other conditions, by suppressing CD47 and / or blocking TSP1 and / or CD47 activity or interaction. Influencing the interaction of CD47-TSP1 in blood vessels allows for control of blood vessel diameter and blood flow, and permits modification of blood pressure and cardiac function. Under conditions of decreased blood flow, for instance through injury or atherosclerosis, blocking TSP1-CD47 interaction allows blood vessels to dilate and increases blood flow, tissue perfusion and tissue survival. This in turn reduces or prevents tissue necrosis and death. The therapeutics identified herein allow for precise regulation of blood flow to tissues and organs which need it, while substantially avoiding systemic complications. Methods and compositions described herein can be used to increase tissue survival under conditions of trauma and surgery, as well as conditions of chronic vascular disease. Also disclosed are methods for the treatment of elderly subjects using agents that affect TSP1 and CD47 and thereby affect tissue perfusion. Additionally, provided herein are compositions and methods for influencing blood coagulation, allowing for controlled increased or decreased blood clotting. Additionally, provided herein are compositions and methods for decreasing blood flow, as in the case of cancer through mimicking the effects of TSP1 and CD47 on blood vessel diameter and blood flow.

Nanosecond pulsed electric field (nsPEF) treatments of a tumor are used to cause the tumor to express calreticulin and stimulate an immune response against the tumor and other tumors in a subject. An immune response biomarker can be measured, and further nsPEF treatments can be performed if needed to stimulate or further stimulate the immune response. Cancers that have metastasized may be treated. The treatment can be combined with CD47-blocking antibodies, doxorubicin, CTLA-4-blocking antibodies, and / or PD-1-blocking antibodies. Electrical characteristics of nsPEF treatments can be based on the size, type, and / or strength of tumors and / or a quantity of tumors in the subject.

Anti-SIRPα antibodies, including multi-specific anti-SIRPα antibodies, are provided, as are related compositions and methods. The antibodies of the disclosure bind to SIRPα and can block the interaction of CD47 on one cell with SIRPα on a phagocytic cell. Antibodies that are bispecific for SIRPα and a second antigen are termed Bi-specific Macrophage Enhancing (BiME) antibodies and have emergent properties. The subject anti-SIRPα antibodies find use in various therapeutic methods. Embodiments of the disclosure include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the anti-SIRPα antibodies; and cell lines that produce the antibodies. Also provided are amino acid sequences of exemplary anti-SIRPα antibodies.

Methods are provided to manipulate phagocytosis of cells, including hematopoietic cells, e.g. circulating hematopoietic cells, bone marrow cells, etc.; and solid tumor cells. In some embodiments of the invention the circulating cells are hematopoietic stem cells, or hematopoietic progenitor cells, particularly in a transplantation context, where protection from phagocytosis is desirable. In other embodiments the circulating cells are leukemia cells, particularly acute myeloid leukemia (AML), where increased phagocytosis is desirable.

Provide herein are fusion polypeptides that comprise a CD47 extracellular domain or a variant thereof that is fused to a Fc polypeptide. The fusion polypeptides are useful for treating an immunological disease or disorder in a subject according to the methods described herein. The fusion polypeptides are capable of suppressing immunoresponsiveness of an immune cell, inhibiting production of proinflammatory cytokines, including inhibiting immune complex-induced production of cytokines.

The invention discloses bispecific recombinant protein. The bispecific recombinant protein comprises a high-affinity tumor-targeted arm and a low-affinity fusion protein for blocking interaction of CD47 and SIRPalpha, wherein an antibody corresponding to the high-affinity tumor-targeted arm is not combined with the CD47, and the bonding affinity to target antigens on tumor cells is at least 6 times of the bonding affinity of the monomeric fusion protein and dimer corresponding to the low-affinity fusion protein for blocking the interaction of the CD47 and the SIRPalpha to the CD47 on the tumorcells; the low-affinity fusion protein for blocking mutual action of the CD47 and SIRPalpha contains SIRPalpha extracellular truncation. The invention also discloses a nucleic-acid molecule for encoding the recombinant protein and application of the recombinant protein and the nucleic-acid molecule in preparation of medicines for treating tumors. The bispecific recombinant protein disclosed by the invention has the beneficial effects that the bonding abundance of tumor targeting saturation of the recombinant protein with the function of adjusting macrophage is obviously improved by the bispecific recombinant protein, the side effect of the non-tumor targeting is reduced and the application value is large clinically.

CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRPα / CD47 axis. The agent is a human SIRPα fusion protein that displays negligible CD47 agonism and negligible red blood cell binding. The fusion protein comprises an IgV domain from variant 2 of human SIRPα, and an Fc having effector function. The IgV domain binds human CD47 with an affinity that is at least five fold greater than the affinity of the entire extracellular region of human SIRPα. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

The invention relates to the field of biomedicine, discloses a CD47 nanobody and an application thereof, and particularly discloses a blocking type nanobody for integrin-associated protein (CD47) andderived protein thereof. Particularly, the invention discloses an integrin-associated protein (CD47) binding molecule and an application thereof, particularly in treatment and / or prevention or diagnosis of CD47 associated diseases such as tumor. The related CD47 nanobody can effectively block interaction between the CD47 and a ligand SIRPa thereof, and the antibody cannot cause human erythrocyte agglutination.