Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-D47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.

Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.

Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.

Abstract: Methods are provided for targeting cells for depletion, including without limitation cancer cells, in a regimen comprising contacting the targeted cells with a combination of immunoregulatory agents. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.

Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-CD47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.

Abstract: Methods are provided for targeting cells for depletion, including, without limitation, cancer cells, in a regimen comprising contacting the targeted cells with a combination of agents, including (i) an agent that blockades CD47 activity; and (ii) an antibody that specifically binds to EGFR. In some embodiments the cancer cells have a mutated form of one or more of KRAS, NRAS and BRAF. The level of depletion of the targeted cell is enhanced relative to a regimen in which a single agent is used; and the effect may be synergistic relative to a regimen in which a single agent is used.

Abstract: Methods, kits, and compositions are provided herein that can be used to treat CD20+ cancer using an anti-CD47 agent such as an antibody. The anti-CD47 agent can be used alone or in combination with one or more additional agent such as an anti-CD20 antibody.

Abstract: Methods, kits, and compositions are provided herein that can be used to treat ovarian cancer using an anti-CD47 antibody. The anti-CD47 antibody can be used alone or in combination with one or more additional agent such as chemotherapy.

Abstract: Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD4 7 blockade.

Abstract: Methods, kits, and compositions are provided herein that can be used to treat CD20+ cancer using an anti-CD47 agent such as an antibody. The anti-CD47 agent can be used alone or in combination with one or more additional agent such as an anti-CD20 antibody.

Abstract: Methods are provided for treating a subject with an anti-CD47 agent.

Abstract: Provided herein are signal-regulatory protein ? (SIRP?) fusion polypeptides comprising modified Fc domains, and methods of making and use thereof. The inclusion of the modified Fc domains results in pharmacokinetic and/or phamacodynamic improvements to the SIRP? fusion polypeptides. The compositions and methods described herein may be used to treat a variety of diseases, such as cardiovascular disease.

Abstract: Methods, kits, and compositions are provided herein that can be used to treat ovarian cancer using an anti-CD47 antibody. The anti-CD47 antibody can be used alone or in combination with one or more additional agent such as chemotherapy.

Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.

Abstract: Therapeutic and diagnostic methods are provided, which methods relate to the induction of expression of calreticulin on phagocytic cells. Specifically, the methods relate to macrophage-mediated programmed cell removal (PrCR), the methods comprising increasing PrCR by contacting a phagocytic cell with a toll-like receptor (TLR) agonist; or down-regulating PrCR by contacting a phagocytic cell with an inhibitor of Bruton's tyrosine kinase (BTK). In some embodiments, an activator of TLR signaling or a BTK agonist is provided in combination with CD4 7 blockade.

Abstract: Anti-SIRP? antibodies, including multi-specific anti-SIRP? antibodies, are provided, as are related compositions and methods. The antibodies of the disclosure bind to SIRP? and can block the interaction of CD47 on one cell with SIRP? on a phagocytic cell.

Abstract: Methods are provided herein for determining and administering optimized dosing of therapeutic anti-CD47 agents, in a schedule that provides safe escalation of dose while achieving a therapeutic level in a clinically effective period of time. The methods can comprise the steps of clearance, escalation, and maintenance. In one embodiment the dosing regimen administers an initial (i) sub-therapeutic dose of an anti-CD47 agent or (ii) a cytoreductive therapy to achieve a safe level of circulating tumor cells for subsequent treatment (clearance); escalating the dose of an anti-CD47 agent until a therapeutic dose is reached (escalation); and maintaining the therapeutic dose for a period of time sufficient to reduce tumor cells in the bone marrow of the patient (maintenance). In an alternative dosing regimen, a patient determined to have a safe level of circulating tumor cells at presentation is treated by the steps of escalation and maintenance without initial clearance.

Abstract: Methods are provided for treating a subject with an anti-CD47 agent.

Abstract: Anti-SIRP? antibodies, including multi-specific anti-SIRP? antibodies, are provided, as are related compositions and methods. The antibodies of the disclosure bind to SIRP? and can block the interaction of CD47 on one cell with SIRP? on a phagocytic cell. The subject anti-SIRP? 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-SIRP? antibodies; and cell lines that produce the antibodies. Also provided are amino acid sequences of exemplary anti-SIRP? antibodies.

Abstract: Methods are provided for treating a subject with a therapeutic dose of anti-CD47 agent by administering a primer agent prior to administering a therapeutically effective dose of an anti-CD47 agent to the subject.