MACROPHAGE STIMULATION IN CD47 BLOCKADE THERAPY
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.
1 . A method for depleting CD47+ disease cells in a subject in need thereof, comprising administering, to the subject, a SIRPαFc drug and a macrophage stimulating agent.
2 . (canceled)
3 . The method according to claim 1 , wherein the macrophage stimulating agent is a TLR agonist.
4 . The method according to claim 3 , wherein the TLR agonist is selected from lipopolysaccharide (LPS), Resiquimod, and poly(I:C).
5 . (canceled)
6 . The method according to claim 1 , wherein the macrophage stimulating agent comprises at least one protein selected from macrophage colony stimulating factor (M-CSF), granulocyte macrophage colony stimulating factor (GM-CSF), heat aggregated gamma globulin (HAGG), tumour necrosis factor alpha (TNFα), and transforming growth factor beta (TGFβ).
7 . The method according to claim 1 , wherein the macrophage stimulating agent comprises an interferon selected from interferon gamma and interferon alpha.
8 . The method according to claim 1 , wherein the macrophage stimulating agent comprises an interleukin selected from IL-1β, IL-4, and IL-10, and mixtures thereof.
9 . (canceled)
10 . The method according to claim 1 , wherein the SIRPαFc drug comprises an Fc based on IgG1.
11 . The method according to claim 1 , wherein the SIRPαFc drug comprises an Fc based on IgG4.
12 . The method according to claim 10 , wherein the SIRPαFc drug comprises the amino acid sequence of SEQ ID NO: 3.
13 . The method according to claim 11 , wherein the SIRPαFc drug comprises the amino acid sequence of SEQ ID NO: 8.
14 . (canceled)
15 . In combination in unit dosage form for depleting CD47+ disease cells in a subject in need thereof, a SIRPαFc drug effective for depleting CD47+ disease cells, and a macrophage stimulating agent effective for enhancing said depletion of CD47+ disease cells.
16 . (canceled)
17 . The method according to claim 1 , wherein the CD47+ disease cells are CD47+ cancer cells.
18 . The method according to claim 17 , wherein the CD47+ cancer cells are CD47+ blood cancer cells.
19 . The method according to claim 18 , wherein the CD47+ cancer cells are cells of a cancer type selected from acute lymphocytic leukemia (ALL); acute myeloid leukemia (AML); chronic lymphocytic leukemia (CLL); chronic myelogenous leukemia (CML); myeloproliferative disorder/neoplasm (MPDS), mycosis fungoides; and myelodysplastic syndrome.
20 . The method according to claim 19 , wherein the cancer is a lymphoma selected from a Hodgkin's lymphoma, both indolent and aggressive non-Hodgkin's lymphoma, Burkitt's lymphoma, small cell follicular lymphoma and large cell follicular lymphoma.
21 . The method according to claim 20 , wherein the cancer is a myeloma selected from multiple myeloma (MM), giant cell myeloma, heavy-chain myeloma, and light chain or Bence-Jones myeloma.
22 . The method according to claim 1 , wherein the subject has a CD47+ cancer, and wherein the macrophage stimulating agent comprises interferon gamma 1 b or interferon alpha 2a.
23 .- 24 . (canceled)
25 . The combination in unit dosage form according to claim 15 , wherein the SIRPαFc drug comprises SEQ ID NO: 3.
26 . (canceled)
27 . The combination in unit dosage form according to claim 15 , wherein the SIRPαFc drug comprises SEQ ID NO: 8.
28 .- 29 . (canceled)
30 . A method of enhancing the anti-cancer effect of a SIRPαFc drug, the method comprising administering, to a subject receiving said SIRPαFc drug, a macrophage stimulating agent.