Compositions and methods to enhance the immune system

• US 9,352,037 B2
• Filed: 01/13/2014
• Issued: 05/31/2016
• Est. Priority Date: 04/23/2008
• Status: Active Grant

• Current Assignee: Stichting Sanquin Bloedvoorziening
• Original Assignee: Stichting Sanquin Bloedvoorziening
• Inventors: van den Berg, Timo Kars
• Primary Examiner(s): CANELLA, KAREN A
• Application Number:
  US14/153,714
• Publication Number:
  US 20140199308A1
• Time in Patent Office: 869 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/507 Comprising a combination of two or more separate antibodies
• CPC Class Codes: A61K 2039/57 characterised by the type of response, e.g. Th1, Th2
• CPC Class Codes: A61K 2039/572 cytotoxic response
• CPC Class Codes: A61K 39/12 Viral antigens
• CPC Class Codes: A61K 39/275 Poxviridae, e.g. avipoxvirus
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/14 for RNA viruses
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2863 against receptors for growth factors, growth regulators
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/2893 against CD52
• CPC Class Codes: C07K 16/30 from tumour cells
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/77 : Internalization into the cell
• CPC Class Codes: C12N 2710/24034 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein
• CPC Class Codes: C12N 2710/24134 : Use of virus or viral component as vaccine, e.g. live-attenuated or inactivated virus, VLP, viral protein

Abstract

The invention relates to the field of molecular medicine. In particular, it relates to compositions and methods to enhance the clearance of aberrant cells, e.g. cancer cells or virus-infected cells, by the host'"'"'s immune system. Provided is a composition comprising (i) a therapeutic compound that can trigger a host'"'"'s immune effector cells against an aberrant cell, such as a therapeutic antibody, and (ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPalpha.

Claims

1. A composition comprising

(i) a therapeutic compound that can trigger a host'"'"'s immune effector cells against a cancer cell, wherein said therapeutic compound is a therapeutic antibody comprising a human or non-human primate IgG Fc portion, wherein the therapeutic antibody induces antibody-dependent cellular cytotoxicity (ADCC), and wherein the therapeutic antibody is selected from the group consisting of rituximab, herceptin, trastuzumab, alemtuzumab, bevacizumab, cetuximab and panitumumab, and

(ii) at least one agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα

, wherein said agent is an anti-CD47 antibody or an anti-SIRPα

antibody or a Fab fragment, a F(ab′

)2 fragment or a scFv fragment thereof.

2. A method of enhancing in vivo efficacy of a therapeutic antibody to induce cancer cell destruction by ADCC in a subject receiving anti-cancer treatment with a therapeutic antibody comprising a human or non-human primate IgG Fc portion, wherein the therapeutic antibody induces antibody-dependent cellular cytotoxicity (ADCC), said method comprising administering to said subject prior to, simultaneously or after the administration of the therapeutic antibody, an agent capable of reducing or preventing inhibitory signal transduction initiated via SIRPα

, wherein the agent is in an amount sufficient to increase ADCC such that the in vivo efficacy of the therapeutic antibody to induce cancer cell destruction by ADCC is enhanced, and wherein said agent is an anti-CD47 antibody or an anti-SIRPα

antibody or a Fab fragment, a F(ab′

)2 fragment or a scFv fragment thereof.