IL-31 Improves Efficacy of Macrophage-Based Adoptive Cell Therapy for Cancer
AssigneeOncoHost Ltd.
InventorMorris C. Laster
Life of this patent
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Abstract
The present invention provides macrophages genetically modified to express IL-31 or both IL-31 and a chimeric antigen receptor (CAR) for treatment of cancer. It further provides methods for treatment of cancer comprising administration of IL-31 along with genetically unmodified macrophages or genetically modified to express a CAR.
Claims20
Macrophages which are genetically modified to express (i) human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1;
- or (ii) a fused protein comprising human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1, wherein in the fused protein the human IL-31 or peptide is attached to an immunoglobulin amino acid sequence comprising IgG.
Method for treating cancer comprising administering to a patient in need a therapeutically effective amount of genetically unmodified macrophages along with an infusion of:
- (i) human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1;
- (ii) a fused protein comprising human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1, wherein in the fused protein the human IL-31 or peptide is attached to an immunoglobulin amino acid sequence comprising IgG:
- or (iii) a complex comprising human IL-31 or a fused protein comprising human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1 and a non-proteinaceous or proteinaceous moiety selected from polyethylene glycol (PEG), polyvinyl pyrrolidone (PVP), divinyl ether, albumin, maleic anhydride copolymer (DIVEMA), polysialic acid (PSA), poly (styrene comaleic anhydride) (SMA), hyaluronic acid (HA), alginic acid (AA), polyhydroxyethyl methacrylate (Poly-HEMA), glyme or polyisopropylacrylamide.
Macrophages which are genetically modified to express a chimeric antigen receptor (CAR) that is designed to be expressed in an immune effector cell, such that the macrophages expressing the CAR possess targeted effector activity including phagocytosis, targeted cellular cytotoxicity, antigen presentation and cytokine secretion.
Macrophages which are genetically modified to express both:
- (i) human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1 or a fused protein comprising human IL-31 of the sequence as set forth in SEQ ID No. 1 or peptide which is at least about 70% homologous to the IL-31 sequence as set forth in SEQ ID No. 1, wherein in the fused protein the human IL-31 or peptide is attached to an immunoglobulin amino acid sequence comprising IgG;
- and (ii) a chimeric antigen receptor (CAR) that is designed to be expressed in immune effector cells, such that the macrophages expressing the CAR possess targeted effector activity, and wherein the CAR comprises an extracellular antigen-binding domain, a transmembrane domain and an intracellular domain.
(canceled)
Dependencies are inferred from the claim text.