189 results about "Macrophage colony-stimulating factor" patented technology

Hybridoma lines that secrete human monoclonal antibodies with high binding specificity and biological activity, particularly neutralizing activity against granulocyte-macrophage colony stimulating factor, and methods of generating the hybridoma lines are provided. Target antigens and epitopes are also provided. The antibodies may be used in therapeutic methods, for example in the treatment of cancer, infectious disease, or autoimmune disease.

The present invention provides a human monoclonal antibody, and antigen-binding portions thereof, capable of binding to human granulocyte-macrophage colony stimulating factor (hGM-CSF) and neutralizing the bioactivity of the hGM-CSF, wherein the anti-hGM-CSF monoclonal antibody has a light chain (L chain) including an amino acid sequence SEQ ID NO:1 and a heavy chain (H chain) including an amino acid sequence SEQ ID NO: 2. Also provided are human monoclonal anti-hGM-CSF antibodies, and antigen-binding portions thereof, characterized by complementarity determining regions (CDRs) or H chain and L chain variable regions related to SEQ ID NO:1 and SEQ ID NO:2. Antibodies, and antigen-binding portions thereof, of the invention are useful in the treatment of diseases associated with overproduction of hGM-CSF, including allergic disease, graft rejection and graft-versus-host disease (GVHD), and autoimmune diseases.

The present invention relates to isolated and purified Magmas protein, isolated and purified nucleic acids encoding Magmas protein, and antibodies to Magmas protein, which interacts with granulocyte macrophage colony stimulating factor (GM-CSF). More specifically, the invention relates to uses of such anti-Magmas antibodies. The invention further relates to a method for diagnosis, prognosis and treatment of diseases, particularly, cancer, Alzheimer's disease and mitochondrial diseases using Magmas sequences and antibodies directed against the Magmas protein or fragments thereof.

A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and / or increase in one or more tryptophan metabolites within the local macrophage microenvironment. Studies demonstrate that expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and therefore other types of transplantation, and that inhibitors of IDO can be used to activate T cells and therefore enhance T cell activation when the T cells are suppressed by pregnancy, malignancy or a virus such as HIV. Inhibiting tryptophan degradation (and thereby increasing tryptophan concentration while decreasing tryptophan metabolite concentration), or supplementing tryptophan concentration, can therefore be used in addition to, or in place of, inhibitors of IDO. Similarly, increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. Although described particularly with reference to IDO regulation, one can instead manipulate local tryptophan concentrations, and / or modulate the activity of the high affinity tryptophan transporter, and / or administer other tryptophan degrading enzymes. Regulation can be further manipulated using cytokines such as macrophage colony stimulating factor, interferon gamma, alone or in combination with antigen or other cytokines.

The present invention relates to immuno-protected encapsulated cells producing an immunomodulator, for example GM-CSF (granulocyte-macrophage colony stimulating factor). The cells of the invention are particularly well adapted for providing an active adjuvant or immunomodulator, for example in the context of immunisation in humans and animals. These cells can be used for vaccination where they provide the immunomodulator in an active form, in a continuous, non-immunogenic manner in the immediate vicinity of the vaccine antigen(s). The invention also relates to a vaccine composition comprising immuno-protected encapsulated cells producing an immunomodulator and an antigenic component. The invention also relates to a kit comprising a cell as described and an antigenic component. The strategy of the invention is perfectly suited for both cancer immunotherapy and vaccination against infectious agents.

The invention relates to the synthetic gene coding for hG-CSF which enables expression in E. coli with an improved expression level of the recombinant hG-CSF regarding the total cellular proteins after expression.

A mechanism of macrophage-induced T cell suppression is the selective elimination of tryptophan and / or increase in one or more tryptophan metabolites within the local macrophage microenvironment. Studies demonstrate that expression of IDO can serve as a marker of suppression of T cell activation, and may play a significant role in allogeneic pregnancy and therefore other types of transplantation, and that inhibitors of IDO can be used to activate T cells and therefore enhance T cell activation when the T cells are suppressed by pregnancy, malignancy or a virus such as HIV. Inhibiting tryptophan degradation (and thereby increasing tryptophan concentration while decreasing tryptophan metabolite concentration), or supplementing tryptophan concentration, can therefore be used in addition to, or in place of, inhibitors of IDO. Similarly, increasing tryptophan degradation (thereby, decreasing tryptophan concentration and increasing tryptophan metabolite concentration), for example, by increasing IDO concentration or IDO activity, can suppress T cells. Although described particularly with reference to IDO regulation, one can instead manipulate local tryptophan concentrations, and / or modulate the activity of the high affinity tryptophan transporter, and / or administer other tryptophan degrading enzymes. Regulation can be further manipulated using cytokines such as macrophage colony stimulating factor, interferon gamma, alone or in combination with antigen or other cytokines.

A flaviviral replicon-based construct is provided for delivery and expression of granulocyte-macrophage colony stimulating factor to facilitate tumour therapy. In particular, the replicon construct encodes a Kunjin virus replicon having one or more mutations in an NS2A non-structural protein that induce enhanced levels of cellular IFN that synergize with recombinant granulocyte-macrophage colony stimulating factor delivered according to the invention. The construct may be administered intra-tumourally or peri-tumourally to an animal as DNA, RNA or packaged into a VLP, for the therapeutic and / or prophylactic treatment of tumours and cancers such as melanoma, lung carcinoma, cervical carcinoma, lung epithelial carcinoma, prostate cancer, breast cancer, renal carcinoma, colon cancer, epithelial cancers and mesothelioma.