Abstract: Materials and methods useful for therapy, including cancer therapy, that combine an agent that blocks the CD47/SIRP? interaction with a DHFR inhibitor are provided.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blocking agent and a CD38 antibody such as daratumumab. The anti-cancer effect of SIRP?Fc is enhanced in the presence of daratumumab. Specific combinations include SIRP?Fc forms that comprise an Fc that is either IgG1 or IgG4 isotype. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a histone deacetylase (HDAC) inhibitor. The anti-cancer effect of one drug enhances the anti-cancer effect of the other. Specific combinations include SIRP?Fc as CD47 blockade drug, and one of depsipeptide and romidepsin as HDAC inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a proteasome inhibitor. The anti-cancer effect of one drug enhances the 5 anti-cancer effect of the other. Specific combinations include SIRP?Fc as CD47 blockade drug, and one of bortezomib, ixazomib and carfilzomib as proteasome inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47? disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a proteasome inhibitor. The anti-cancer effect of one drug enhances the 5 anti-cancer effect of the other. Specific combinations include SIRP?Fc as CD47 blockade drug, and one of bortezomib, ixazomib and carfilzomib as proteasome inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRP?/CD47 axis. The agent is a human SIRP? 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 SIRP?, 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 SIRP?. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blocking agent and an EGFR antibody such as cetuximab. The anti-cancer effect of cetuximab is enhanced in the presence of SIRP?Fc. Specific combinations include SIRP?Fc forms that comprise an Fc that is either IgGl or preferably IgG4 isotype. These combinations are useful particularly to treat solid tumours and blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blocking agent and a CD38 antibody such as daratumumab. The anti-cancer effect of SIRP?Fc is enhanced in the presence of daratumumab. Specific combinations include SIRP?Fc forms that comprise an Fc that is either IgG1 or IgG4 isotype. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRP?/CD47 axis. The agent is a human SIRP? 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 SIRP?, 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 SIRP?. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Abstract: CD47+ disease cells, such as various cancers, are treated using a combination of CD47 blockade with T cell checkpoint inhibition. Preferred embodiments use SIRP?Fc in combination with a PD-1 pathway inhibitor such as nivolumab and/or a CTLA-4 inhibitor such as ipilimumab.

Abstract: CD47+ disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a histone deacetylase (HDAC) inhibitor. The anti-cancer effect of one drug enhances the anti-cancer effect of the other. Specific combinations include SIRP?Fc as CD47 blockade drug, and one of depsipeptide and romidepsin as HDAC inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: CD47? disease cells such as cancer cells are treated using a combination of CD47 blockade drug and a proteasome inhibitor. The anti-cancer effect of one drug enhances the 5 anti-cancer effect of the other. Specific combinations include SIRP?Fc as CD47 blockade drug, and one of bortezomib, ixazomib and carfilzomib as proteasome inhibitor. These combinations are useful particularly to treat blood cancers including lymphomas, leukemias and myelomas.

Abstract: Blockade of the CD47/SIRPa pathway depletes cancer cells. This anti-cancer activity is enhanced when macrophage stimulating agents are used in combination with the CD47 blockade drug. This anti-cancer combination therapy is particularly effective when the CD47 blockade drug is SIRPaFc.

Abstract: CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRP?/CD47 axis. The agent is a human SIRP? 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 SIRP?, 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 SIRP?. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Abstract: CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRP?/CD47 axis. The agent is a human SIRP? 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 SIRP?, 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 SIRP?. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Abstract: CD47+ disease cells, such as CD47+ cancer cells, are treated with an agent that blocks signalling via the SIRP?/CD47 axis. The agent is a human SIRP? 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 SIRP?, 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 SIRP?. The fusion protein is at least 5 fold more potent than a counterpart lacking effector function.

Abstract: The present invention provides reagents and methods for producing and utilizing targeted immunogens. In preferred embodiments, an immunogen is conjugated to an amino acid sequence that targets the immunogen to the MHC presentation pathway. Using the reagents and methods provided herein, immunization protocols may be enhanced resulting in increased immunity of the host.