US2016361415A1PendingUtilityA1

Methods of Using Interleukin-10 for Treating Diseases and Disorders

59
Assignee: ARMO BIOSCIENCES INCPriority: May 28, 2015Filed: May 26, 2016Published: Dec 15, 2016
Est. expiryMay 28, 2035(~8.9 yrs left)· nominal 20-yr term from priority
Inventors:John Brian MummIvan Ho Chan
A61K 9/0019A61K 2039/55527C07K 2319/03C07K 16/30C07K 2317/73A61K 39/39A61P 37/02A61K 38/2066A61P 43/00A61K 47/60C12N 2310/14A61K 39/39558C07K 14/7051C12N 15/1136A61P 35/00C07K 2319/02A61K 47/48215A61K 2039/5158
59
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Claims

Abstract

Methods of modulating immune responses in subjects having oncology- and immune-related diseases, disorders and conditions by the administration of an IL-10 agent, including pegylated IL-10.

Claims

exact text as granted — not AI-modified
1 . A method of modulating a T cell-mediated immune response to a target cell population in a subject, comprising:
 a) introducing to the subject a therapeutically effective plurality of cells genetically modified to express a chimeric antigen receptor (CAR),   wherein the chimeric antigen receptor comprises at least one antigen-specific targeting region capable of binding to the target cell population, and   wherein the binding of the chimeric antigen receptor targeting region to the target cell population is capable of eliciting activation-induced cell death; and   b) administering to a the subject a therapeutically effective amount of an IL-10 agent sufficient to prevent or limit the activation-induced cell death,   thereby modulating the T-cell-mediated immune response.   
     
     
         2 . (canceled) 
     
     
         3 . (canceled) 
     
     
         4 . The method of  claim 1 , wherein the CAR comprises an antigen binding domain which specifically recognizes the target cell population. 
     
     
         5 . The method of  claim 1 , wherein the CAR further comprises a transmembrane domain and a signaling domain. 
     
     
         6 . The method of  claim 5 , wherein the signaling domain comprises a CD3 zeta signaling domain. 
     
     
         7 . The method of  claim 5 , wherein the signaling domain comprises at least one co-stimulatory domain. 
     
     
         8 . The method of  claim 1 , wherein the IL-10 agent enhances the function of activated memory CD8+ T cells. 
     
     
         9 . The method of  claim 1 , wherein administration of the IL-10 agent is prior to administration of the therapeutically effective plurality of cells. 
     
     
         10 . The method of  claim 1 , wherein administration of the IL-10 agent is simultaneously with administration of the therapeutically effective plurality of cells. 
     
     
         11 . The method of  claim 1 , wherein administration of the IL-10 agent is subsequent to the administration of the therapeutically effective plurality of cells. 
     
     
         12 .- 19 . (canceled) 
     
     
         20 . The method of  claim 1 , wherein the amount of the IL-10 agent administered is sufficient to enhance cytotoxic function. 
     
     
         21 . The method of  claim 20 , wherein the amount of the IL-10 agent administered is sufficient to achieve a serum concentration of 10-100 ng/mL. 
     
     
         22 . The method of  claim 1 , wherein the IL-10 agent is a PEG-IL-10. 
     
     
         23 . The method of  claim 22 , wherein the PEG-IL-10 comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one monomer of IL-10. 
     
     
         24 . The method of  claim 22 , wherein the PEG-IL-10 comprises a mixture of mono-pegylated and di-pegylated IL-10. 
     
     
         25 . The method of  claim 22 , wherein the PEG component of the PEG-IL-10 has a molecular mass from 5 kDa to 20 kDa. 
     
     
         26 . The method of  claim 22 , wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 20 kDa. 
     
     
         27 . The method of  claim 22 , wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 30 kD. 
     
     
         28 . The method of  claim 1 , wherein the IL-10 agent is administered subcutaneously. 
     
     
         29 . The method of  claim 1 , wherein the plurality of cells is obtained from the subject and genetically modified ex vivo. 
     
     
         30 . The method of  claim 29 , wherein the plurality of cells is obtained from the subject by apheresis. 
     
     
         31 . - 33 . (canceled) 
     
     
         34 . The method of  claim 30 , wherein the plurality of cells are memory CD8+ T cells. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . The method of  claim 1 , wherein the plurality of cells are autologous tumor cells. 
     
     
         38 . (canceled) 
     
     
         39 . The method of  claim 1 , wherein the target cell population comprises a tumor antigen. 
     
     
         40 . The method of  claim 39 , wherein the tumor antigen is selected from the group consisting of CD19, CD20, CD22, ROR1, mesothelin, CD33/IL3Ra, c-Met, PSMA, Glycolipid F77, EGFRvIII, GD-2, NY-ESO-1 TCR, MAGE A3 TCR, or any combination thereof. 
     
     
         41 . A method of treating a subject having a cancer-related disease, disorder or condition, comprising:
 a) introducing to the subject a therapeutically effective plurality of cells genetically modified to express a chimeric antigen receptor (CAR),   wherein the chimeric antigen receptor comprises at least one antigen-specific targeting region capable of binding to the target cell population, and   wherein the binding of the chimeric antigen receptor targeting region to the target cell population is capable of eliciting activation-induced cell death; and   b) administering to the subject a therapeutically effective amount of an IL-10 agent sufficient to prevent or limit the activation-induced cell death.   
     
     
         42 . (canceled) 
     
     
         43 . (canceled) 
     
     
         44 . The method of  claim 41 , wherein the CAR comprises an antigen binding domain which specifically recognizes the target cell population. 
     
     
         45 . The method of  claim 41 , wherein the CAR further comprises a transmembrane domain and a signaling domain. 
     
     
         46 . The method of  claim 45 , wherein the signaling domain comprises a CD3 zeta signaling domain. 
     
     
         47 . The method of  claim 45 , wherein the signaling domain comprises at least one co-stimulatory domain. 
     
     
         48 . The method of  claim 41 , wherein the IL-10 agent enhances the function of activated memory CD8+ T cells. 
     
     
         49 . The method of  claim 41 , wherein administration of the IL-10 agent is prior to administration of the therapeutically effective plurality of cells. 
     
     
         50 . The method of  claim 41 , wherein administration of the IL-10 agent is simultaneously with administration of the therapeutically effective plurality of cells. 
     
     
         51 . The method of  claim 41 , wherein administration of the IL-10 agent is subsequent to the administration of the therapeutically effective plurality of cells. 
     
     
         52 .- 59 . (canceled) 
     
     
         60 . The method of  claim 41 , wherein the amount of the IL-10 agent administered is sufficient to enhance cytotoxic function. 
     
     
         61 . The method of  claim 60 , wherein the amount of the IL-10 agent administered is sufficient to achieve a serum concentration of 10-100 ng/mL. 
     
     
         62 . The method of  claim 41 , wherein the IL-10 agent is a PEG-IL-10. 
     
     
         63 . The method of  claim 62 , wherein the PEG-IL-10 comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one monomer of IL-10. 
     
     
         64 . The method of  claim 62 , wherein the PEG-IL-10 comprises a mixture of mono-pegylated and di-pegylated IL-10. 
     
     
         65 . The method of  claim 62 , wherein the PEG component of the PEG-IL-10 has a molecular mass from 5 kDa to 20 kDa. 
     
     
         66 . The method of  claim 62 , wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 20 kDa. 
     
     
         67 . The method of  claim 62 , wherein the PEG component of the PEG-IL-10 has a molecular mass of at least 30 kD. 
     
     
         68 . The method of  claim 41 , wherein the IL-10 agent is administered subcutaneously. 
     
     
         69 . The method of  claim 41 , wherein the plurality of cells is obtained from the subject and genetically modified ex vivo. 
     
     
         70 . The method of  claim 69 , wherein the plurality of cells is obtained from the subject by apheresis. 
     
     
         71 .- 73 . (canceled) 
     
     
         74 . The method of  claim 70 , wherein the plurality of cells are memory CD8+ T cells. 
     
     
         75 .- 76 . (canceled) 
     
     
         77 . The method of  claim 41 , wherein the plurality of cells are autologous tumor cells. 
     
     
         78 . (canceled) 
     
     
         79 . The method of  claim 41 , wherein the target cell population comprises a tumor antigen. 
     
     
         80 .- 89 . (canceled) 
     
     
         90 . A method of enhancing the function of a CAR-T T cell, comprising:
 a) genetically engineering a T cell to express a CAR, thereby generating a CAR-T T cell; and   b) modulating the CAR-T T cell with an agent that reduces the amount of at least one cytokine secreted by the CAR-T T cell,   thereby enhancing the function of the CAR-T T cell.   
     
     
         91 . The method of  claim 90 , wherein the agent is a small interfering RNA (siRNA). 
     
     
         92 . The method of  claim 91 , wherein the cytokine is a member of the tumor necrosis factor family or the transforming growth factor beta superfamily. 
     
     
         93 . The method of  claim 92 , wherein the member of the tumor necrosis factor family is TNFα. 
     
     
         94 . The method of  claim 92 , wherein the member of the transforming growth factor beta superfamily is TGF-β. 
     
     
         95 . The method of  claim 94 , wherein reducing the amount of TGF-β reduces the proliferation of T regulatory cells.

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