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 or 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: The invention provides genetically modified hematopoietic stem or progenitor cells (HSPCs) and methods of using the HSPCs in stem cell replacement therapy. The HSPCs are genetically modified to express a receptor conferring a selective advantage on the introduced cells relative to endogenous HSPCs or a control HSPCs without the modification. The presence of such a receptor provides resistance to an immunotherapy regime used for eliminating endogenous HSPCs.

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 enhancing immunization strategies by manipulation, e.g. in vitro manipulation, of phagocytic antigen presenting cells. In the methods of the invention, phagocytic antigen presenting cells (phAPC) are incubated with a particulate antigen in the presence of an anti-CD47 agent in a dose and for a period of time sufficient to allow the phAPC to phagocytose the particulate antigen, which process generates a “loaded” phAPC. The loaded phAPC is contacted with a population of T cells matched for at least one major histocompatibility locus with the phAPC, where the T cells are stimulated after contacting to generate an effector response against an epitope or epitopes present on the particulate antigen.

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 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 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 or 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 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: 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: 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 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 individuals with ovarian cancers with an anti-CD47 antibody and an anti PD-L1 antibody.

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: The invention provides co-administration regimes of immunotherapeutic agents specifically binding to c-kit or inhibiting CD47-SIRP? for ablation of endogenous HSPCs. Relatively low levels of anti-c-kit result in saturation of binding to c-kit on HSPCs without significant reduction of the levels HSPCs. Significant reduction of the level of HSPCs can be obtained when the action of anti-c-kit is promoted by an immunotherapeutic agent inhibiting CD47-SIRP?. HSPCs expressing c-kit can thus be reduced to an acceptable level an acceptable level to permit introduction of replacement HSPCs without detrimental delay during which a subject has inadequate HSPCs.

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 CD47 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. Antibodies that are bispecific for SIRP? and a second antigen are termed Bi-specific Macrophage Enhancing (BiME) antibodies and have emergent properties. 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, 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: 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.