44 results about "HLA-G" patented technology

The present invention relates to a skin equivalent and a method for producing the same, wherein the skin equivalent comprises a scaffold and stem / progenitor cells isolated from the amniotic membrane of umbilical cord. These stem / progenitor cells may be mesenchymal (UCMC) and / or epithelial (UCEC) stem cells, which may then be further differentiated to fibroblast and keratinocytes. Further described is a method for isolating stem / progenitor cells from the amniotic membrane of umbilical cord, wherein the method comprises separating the amniotic membrane from the other components of the umbilical cord in vitro, culturing the amniotic membrane tissue under conditions allowing cell proliferation, and isolating the stem / progenitor cells from the tissue cultures. The invention also refers to therapeutic uses of these skin equivalents. Another aspect of the invention relates to the generation of a mucin-producing cell using stem / progenitor cells obtained from the amniotic membrane of umbilical cord and therapeutic uses of such mucin-producing cells. In yet another aspect, the invention relates to a method for generating an insulin-producing cell using stem / progenitor cells isolated from the amniotic membrane of umbilical cord and therapeutic uses thereof. The invention further refers to a method of treating a bone or cartilage disorder using UCMC. Furthermore, the invention refers to a method of generating a dopamin and tyrosin hydroxylase as well as a HLA-G and hepatocytes using UCMC and / or UCEC. The present invention also refers to a method of inducing proliferation of aged keratinocytes using UCMC.

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

The present invention relates to a skin equivalent and a method for producing the same, wherein the skin equivalent comprises a scaffold and stem / progenitor cells isolated from the amniotic membrane of umbilical cord. These stem / progenitor cells may be mesenchymal (UCMC) and / or epithelial (UCEC) stem cells, which may then be further differentiated to fibroblast and keratinocytes. Further described is a method for isolating stem / progenitor cells from the amniotic membrane of umbilical cord, wherein the method comprises separating the amniotic membrane from the other components of the umbilical cord in vitro, culturing the amniotic membrane tissue under conditions allowing cell proliferation, and isolating the stem / progenitor cells from the tissue cultures. The invention also refers to therapeutic uses of these skin equivalents. Another aspect of the invention relates to the generation of a mucin-producing cell using stem / progenitor cells obtained from the amniotic membrane of umbilical cord and therapeutic uses of such mucin-producing cells. In yet another aspect, the invention relates to a method for generating an insulin-producing cell using stem / progenitor cells isolated from the amniotic membrane of umbilical cord and therapeutic uses thereof. The invention further refers to a method of treating a bone or cartilage disorder using UCMC. Furthermore, the invention refers to a method of generating a dopamin and tyrosin hydroxylase as well as a HLA-G and hepatocytes using UCMC and / or UCEC. The present invention also refers to a method of inducing proliferation of aged keratinocytes using UCMC.

The invention is directed to novel methods for modulating inflammatory and / or immune responses. Such methods utilize compositions comprising extraembryonic cells (herein referred to as EE cells) including but not limited to extraembryonic HLA-G positive cells (herein referred to as EHP cells) and amnion-derived multipotent progenitor cells (herein referred to as AMP cells); compositions comprising expanded EE cell populations, and / or cell lysates and / or conditioned media derived therefrom, alone or in combination with each other and / or in combination with various extracellular matrices and / or devices and / or other suitable active agents.

Provided herein are compositions comprising anti-HLA-Ib antibodies as IVIg mimetics and methods for using the same for the prevention, treatment, therapy and / or amelioration of inflammation induced diseases and allograft rejection. In certain embodiments, the anti-HLA-Ib antibodies (monoclonal antibodies or mixed monoclonal antibodies, recombinant or chimeric or humanized or human antibodies) strongly mimic IVIg in immunoreactivity to HLA class Ia (HLA-A, HLA-B and HLA-Cw) and Ib antigens (HLA-E, HLA-F and HLA-G). In certain embodiments, the anti-HLA-Ib antibodies (monoclonal or mixed monoclonal antibodies; recombinant, chimeric, humanized or human antibodies) strongly mimic IVIg in immunomodulatory or immunosuppressive activities. While anti-HLA-Ib mAbs can be used to restore anti-tumor activities of CD8+ T cells and Natural killer cells by passive therapy in cancer patients, methods are also provided herein to induce production of polyclonal anti-HLA-Ib antibodies in cancer patients for restoring anti-tumor activities of CD8+ T cells and NK cells, by active specific immunotherapy.

Provided are methods of predicting responsiveness of a subject to interferon treatment, comprising comparing a level of expression in a cell of the subject of at least one gene selected from the group consisting KIR3DL3, KIR3DL2, KIR3DL1, KIR2DL1, KIR2DL2, KIR2DL3, KLRG1, KIR3DS1, CD160, HLA-A, HLA-B, HLA-C, HLA-F, HLA-G and IFI27 to a reference expression data of the at least one gene obtained from at least one interferon responder subject and / or at least one interferon non-responder subject. Also provided are methods and pharmaceutical compositions for treating a subject in need of interferon treatment.

The invention discloses a simple method for detecting HLA-G and antibody thereof by gold-labeled immunoassay. The invention uses the monoclonal antibody of HLA-G and an HLA-G antigen fragment and / or HLA-G for successfully developing a gold-labeled immunity percolation analysis kit, and a gold-labeled immunochromatography sandwich method and competition method kit, which are used for the public to easily, rapidly and cheaply self-check and self-test the HLA-G in body fluid such as blood, saliva, urine, and the like so as to diagnose the early malignant tumor. In order to diagnose the earlier malignant tumor, a kit for detecting the HLA-G antibody by a gold-labeled immunochromatography indirect method is also developed and used for diagnosing the earlier malignant tumor. The kits are all called as 'broad-spectrum tumor diagnostic kit'. The invention aims at developing an easy, rapid and cheap 'broad-spectrum tumor diagnostic kit' for the self-check and self-test of the public so as to realize primary tumor screening and achieve the goal of finding and curing the tumor early, save the lives of the tumor patients, and reduce the tumor mortality.

The invention is directed to novel methods for modulating inflammatory and / or immune responses. Such methods utilize compositions comprising extraembryonic cells (herein referred to as EE cells) including but not limited to extraembryonic HLA-G positive cells (herein referred to as EHP cells) and amnion-derived multipotent progenitor cells (herein referred to as AMP cells); compositions comprising expanded EE cell populations, and / or cell lysates and / or conditioned media derived therefrom, alone or in combination with each other and / or in combination with various extracellular matrices and / or devices and / or other suitable active agents.

The invention discloses an ultra-sensitive method for the chemiluminescence immunoassay detection of HLA-G. The method takes artificially synthesized HLA-G antigen fragment as immunogen immune BALB / c mouse for obtaining a hybridoma cell line. By using the combination of an HLA-G monoclonal antibody which is secreted by the hybridoma cell line with a chemiluminescence immunoassay technology, a broad-spectrum tumor diagnostic kit is formed. The broad-spectrum tumor diagnostic kit is used for the clinical diagnosis of various malignant tumors by detecting the HLA-G. The broad-spectrum tumor diagnostic kit detects the HLA-G by a double monoclonal antibody sandwich method or competition method. The chemiluminescence immunoassay technology uses an enzymatic chemiluminescence method or an acridine ester chemiluminescence method.

It has been discovered that HLA-G dimers are potent ligands of ILT2 and ILT4 on immune cells and enhance signal transduction through ILT2 and ILT4. Enhanced signal transduction through ILT-2, ILT-4 or both down-regulates the biological activity of T cells and dendritic cells. HLA-G compositions including HLA-G dimers are provided that are useful for modulating activity of immune cells. Preferred compositions include microparticles having HLA-G dimers on the surface of the microparticles. The microparticles optionally include a targeting moiety to target the microparticles to specific immune cells. In a preferred embodiment the microparticles are targeted to T cells or dendritic cells expressing ILT2 or both ILT2 and ILT4, respectively. The HLA-G dimer can include any HLA-G protein that is capable of forming a dimer. Preferred HLA-G proteins include HLA-G1 and HLA-G5. In certain embodiments the microparticles include dimers of HLA-G1 and HLA-G5.

The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C / C8, 3C / G4, and 4H84. 2C / C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C / G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

A method for identifying and screening dendritic killer cells (DKC) is disclosed in the present invention, and the method is to identify a plurality of cell surface markers selected from a group consisting of HLA-G−, CD14−, CD3-, CD19−, CD56dim and HLA-DR+. The method for screening DKC from human peripheral blood mononuclear cells (PBMC) comprises the following steps. A first cell population with regular cell size is provided and a second cell population is then sorted out from the first cell population by screening the phenotype of CD14 and HLA-G therein. A third cell group is further sorted out from the second cell population by screening the phenotype of CD19 and CD3 therein. Finally, DKC will be identified out of the third cell population by screening the phenotype of CD56 and HLA-DR.

The present invention relates to the detection of HLA-G. Antibodies to both soluble and membrane bound HLA-G are disclosed. Exemplary antibodies include 2C / C8, 3C / G4, and 4H84. 2C / C8 and 4H84 antibodies bind to the same region of HLA-G, which is a different region than that bound by 3C / G4. Methods of detection and diagnosis are disclosed as well as kits, including a miniaturized assay suitable for a clinical setting. Further, a method of selecting an embryos for in vitro fertilization is disclosed. A sandwich ELISA test is provided using two antibodies that bind to HLA-G at different regions. The HLA-G test according to the invention is over 1000 times more selective in binding to HLA-G than to antigens HLA-A2, HLA-B4, HLA-C, or mixed WBC preparations.

This disclosure provides a multi-specific fusion protein composed of a CD86 antagonist binding domain and another binding domain that is an IL-10 agonist, an HLA-G agonist, an HGF agonist, an IL-35 agonist, a PD-1 agonist, a BTLA agonist, a LIGHT antagonist, a GITRL antagonist or a CD40 antagonist. The multi-specific fusion protein may also include an intervening domain that separates the other domains. This disclosure also provides polynucleotides encoding the multi-specific fusion proteins, compositions of the fusion proteins, and methods of using the multi-specific fusion proteins and compositions.

The invention relates to a pancreatic cancer diagnostic marker and an application thereof. The pancreas cancer diagnosis marker comprises any one or more of protein of HLA-G, POSTN, COL12A1, THBS2, MUC5AC, AGR2, GPRC5A, USP44, CPEB2, DDX19B, CAMP, DUS1L, SLC16A3, ZNF236, TPM4, CHGA, S100P, CEACAM6, S100A12, HTRA3, COL10A1 and LAMC2. The invention also relates to a kit for detecting the expressionlevel of any one or more of these proteins.

The invention relates to a method of using HLA-G positive mesenchymal stem cells to treat systemic lupus erythematosus, in particular to, on one hand, a method of preparing human leukocyte antigen-G positive mesenchymal stem cells for treating systemic lupus erythematosus. The system includes following steps: (1), performing isolated culture on HLA-G+umbilical card mesenchymal stem cells; (2), cryopreserving the HLA-G positive mesenchymal stem cells; (3), resuscitating the HLA-G positive mesenchymal stem cells. Higher than 90% of the mesenchymal stem cells prepared by the method is positive to human leukocyte antigen-G. It has been already found that the HLA-G+umbilical card mesenchymal stem cells have excellent effect on treating systemic lupus erythematosus.

This invention relates to a therapeutic molecule capable of suppressing an immune response against an organ or tissue transplantation in a patient. In particular, the invention relates to a conjugate comprising a first portion connected to a second portion, wherein the first portion binds to an MHC Class I molecule and the second portion has HLA-G activity. This conjugate may be used as a medicament to modulate immune responses and induce immunological tolerance specific to allogenic MHC complexes.

The present invention discloses a cancer diagnostic kit containing the anti-HLA-G monoclonal antibody, and an application thereof. The kit is an enzyme linked immunosorbent cancer diagnostic kit which is prepared with the novel anti-HLA-G monoclonal antibody and the anti-HLA-G monoclonal antibody HGY-2; wherein, the HGY-2 is generated with the hybridoma which is conserved in the Chinese Typical Culture Conservation Center and is numbered as CCTCC NO.C200722. The kit adopts the serum or other body fluid as the detected sample, the operation is convenient, the accuracy rate is high, the patient compliance is excellent, and the kit provides a novel method and means for cancer diagnosis.

The invention relates to a method for jointly detecting sFlt-1 / PLGF and HLA-G for predicting pre-eclampsia. The method comprises the following steps: collecting serum specimen: respectively collecting5-10 ml of venous blood from pregnant women in a pre-eclampsia group and normal pregnant women with same gestational weeks, centrifuging all specimens in a low temperature centrifuge at 3000 rpm for10 min within 4 h, taking the serum and subpackaging in EP tubes, and storing in a refrigerator at minus 80 DEG C for testing; coating: using a 0.05 M PH9.0 carbonate coated buffer solution to diluteantibodies to the protein content of 1-10[mu]g / ml, adding 0.1ml of the diluted antibodies into reaction holes of each polystyrene board, staying overnight at 4 DEG C, discarding the solution in the holes the next day, and washing for 3 times; setting up standard holes and sample holes, washing, and setting up blank holes, negative control holes and positive control holes at the same time; adding enzyme-labeled antibodies; adding 100 [mu]L of horseradish peroxidase-labeled detection antibodies into each of the standard holes and the sample holes except for the blank holes, sealing the reactionholes with microplate sealers, and incubating in a water bath kettle or an incubator at 37 DEG C for 60 min; performing board-washing; adding 50 [mu]L of a substrate A and a substrate B into each of the holes, and measuring OD values of each hole. The method is high in detection specificity and sensitivity.

In the invention, genes that an alpha 1- alpha 3 area of a code HLA-G (Hepatomaliver Antigen Gene) and a CH1-CH3 area of human IgG (Intravenous Gamma Globulin) are recombined, the obtained infusion protein sHLSA-G / IgG is expressed, and the experiment shows that the infusion protein can significantly inhibit reaction of same reactive T cells at nano-mole level and is more effective than an HLA-G individual in a natural state. The inhibition efficiency of the infusion protein is nearly 10 times of that of the HLA-G individual and the infusion protein not only can inhibit the proliferation of same reactive T cells CD8+T, CD4+T cells, generation of same reactive specific CTL (Cytotoxic T Lymphocyte), but also can regulate the expression of surface ILT2 of same reactive CD8+T so as to further promote the inhibition of the infusion protein. The infusion protein and the acceptor have high affinity, high efficiency for inhibiting same T cell response is realized, and the HLA-G is a multi-state rare human component, therefore, the infusion protein immunosuppressive agent can be used as a safe and efficient immunosuppressive agent.

The invention discloses a method for detecting a human leukocyte antigen HLA-G. A protein fragment of an amino acid sequence at the 85-185th position of a heavy chain of the HLA-G serves as an antigen to prepare an antibody 3C4, a protein fragment of an amino acid sequence at the 1-50th position of a light chain of the HLA-G is coupled with KLH to prepare an antibody 3H1 as an antigen, then 3C4 and 3H1 serve as an enzyme-linked immunosorbent assay reagent to detect the HLA-G, the amino acid sequence at the 85-185th position of the heavy chain of the HLA-G is as shown in SEQ ID NO:1, and the amino acid sequence at the 1-50th position of the light chain of the HLA-G is as shown in SEQ ID NO:2. The method is high in detection sensitivity and good in specificity and has good repeatability and accuracy, and therefore a new method is provided for detecting the HLA-G.

Compositions and methods for inducing, enhancing, or promoting an immune response are disclosed. In some embodiments the increased immune response is against an antigen such as a tumor antigen or a viral antigen. Immune responses include activation of cytotoxic T cells to kill cells displaying the antigen. In some embodiments, the methods include contacting cells with an effective amount of a transcription factor A-mitochondrial (TFAM) fusion protein to increase expression of a Major Histocompatibility Complex I (MHC I), reduce expression of HLA-G on the surface of cells, or increase expression of one or more cytokines or chemokines Methods of treating cancer are also disclosed.

The invention is directed to novel methods for modulating inflammatory and / or immune responses. Such methods utilize compositions comprising extraembryonic cells (herein referred to as EE cells) including but not limited to extraembryonic HLA-G positive cells (herein referred to as EHP cells) and amnion-derived multipotent progenitor cells (herein referred to as AMP cells); compositions comprising expanded EE cell populations, and / or cell lysates and / or conditioned media derived therefrom, alone or in combination with each other and / or in combination with various extracellular matrices and / or devices and / or other suitable active agents.

The invention is directed to novel compositions and methods for modulating inflammatory and / or immune responses. Such novel compositions are derived from extraembryonic cells (herein referred to as EE cells) including but not limited to extraembryonic HLA-G positive cells (herein referred to as extraembryonic HLA-G positive or “EHP” cells) and Amnion-derived Multipotent Progenitor cells (herein referred to as AMP cells), alone or in combination with each other and / or in combination with various matrices and / or devices and / or other suitable active agents. The novel methods of modulating inflammatory and / or immune responses utilize such novel compositions.

Disclosed herein are genetically modified cells expressing HLA-G (e.g., cell surface HLA-G) persistently, and nucleic acid compositions useful for generating such genetically modified cells. Also disclosed are cell therapy methods that utilize genetically modified cells that express HLA-G persistently. The HLA-G genetic modifications described herein provide the cells with characteristics of reduced immunogenicity and / or improved immunosuppression, such that these cells have the promise of being universal or improved donor cells for transplants, cellular and tissue regeneration or reconstruction, and other therapies.

The invention provides a noble cell of a human embryonic stem cell for stably expressing HLA-G molecules. Rich cell resources are provided for clinical cellular transplantation, the problem of immunological rejection during the transplantation of the directional noble cell of the human embryonic stem cell in the clinic is solved, and the invention has the profound clinical application value.