213 results about "CD137" patented technology

The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, β2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject. The MHC antigen may be HLA-B7.

The present invention relates to novel methods for preferentially activating and expanding NK cells. The methods utilize the stimulatory effects of IL-15 and CD137 ligand to preferentially expand and activate NK cells in a mixed cell culture comprising NK cells.

The disclosure provides a chimeric antigen receptor (CAR) comprising a) an antigen binding domain of HA22, a transmembrane domain, and an intracellular T cell signaling domain; or b) an antigen binding domain of BL22, a transmembrane domain, and an intracellular T cell signaling domain comprising CD28 and / or CD137. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The present invention relates to novel methods for preferentially activating and expanding NK cells. The methods utilize the stimulatory effects of IL-15 and CD137 ligand to preferentially expand and activate NK cells in a mixed cell culture comprising NK cells.

The invention includes compositions and methods to rapidly isolate and culture cells that are potent for use in adoptive immunotherapy. In one embodiment, the isolated cells of the invention are tumor infiltrating lymphocytes (TIL) that express CD137 (also known as 4-1BB and TNFSFR9).

The invention relates to a preparation method and application of an autologous CAR (chimeric antigen receptor)-T cell. An established CD28-CD137-CD19-CD3 full-length gene is guided into a T-cell of a patient by a CRISPR / Cas9 technology to prepare the CAR-T cell, and the CAR-T cell is subjected to expansion in vitro and then returns in the body of the patient to perform anti-tumor treatment. Compared with the traditional tumor treatment method, the method has the advantages that the method is cell targeted therapy and small in side effect; the gene modified T cell can stably express an antigen binding domain on the surface and identify a target antigen, and does not have MHC limit; and the tumor treatment effect is improved.

The present disclosure provides combinations of immunotherapeutics and methods for treating medical conditions that are characterized by the lack of an effective immune response, for example as would result following a down-regulation of MHC class I, such as in cancer. The immunotherapeutic compositions of the invention, which can be used to treat the medical conditions, include one or more immunostimulatory antibodies or molecules having specificity for CTLA-4, PD-1, PD-L1, PD-L2, CD40, OX40, CD137, GITR, ILT2, or ILT3, or ligands for these molecules (e.g., an isolated fully-human monoclonal antibody) in association with one or more alloantigens, such as, vector(s) capable of expressing protein(s) or peptide(s) that stimulate T-cell immunity against tissues or cells, formulated in a pharmaceutically acceptable carrier. The proteins or peptides may comprise class I major histocompatibility complex (MHC) antigens, β2-microglobulins, or cytokines. The MHC antigen may be foreign to the subject. The MHC antigen may be HLA-B7.

The invention discloses an anti-BCMA chimeric antigen receptor, an encoding gene, a recombinant expression vector and an establishing method and application of the anti-BCMA chimeric antigen receptor, the encoding gene and the recombinant expression vector. The receptor comprises a CD8 leader chimeric receptor signal peptide, a BCMA single-chain antibody heavy chain VH, an Optimal Linker C, a BCMA single-chain antibody light chain VL, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulatory factor and a TCR chimeric receptor T cell activating domain which are sequentially connected in series. In addition, the invention further discloses the encoding gene and the recombinant expression vector of the anti-BCMA chimeric antigen receptor and the establishing method and application of the encoding gene and the recombinant expression vector. The secretion of cell factors and the cytotoxicity in vitro of CAR-T cells can be remarkably improved, and the clinical treatment effect is outstanding.

The present invention discloses a chimeric antigen receptor, a gene and a recombinant expression vector thereof, an engineered CD19 targeting NKT cell and applications thereof. The chimeric antigen receptor is CD19ScFv-CD8-CD137-CD3 zeta, and consists of a hinge region and a transmembrane region of the CD19ScFv and CD8, an intracellular signal structural domain of CD137, and an intracellular signal structural domain of CD3 zeta, and the the hinge region, the transmembrane region, the intracellular signal structural domain of CD137 and the intracellular signal structural domain of CD3 zeta are connected in series. When used to treat advanced stage CD19-positive B-cell acute lymphocytic leukemia, the NKT cell modified by the chimeric antigen receptor CD19ScFv-CD8-CD137-CD3 zeta provided by the present invention has good specific killing activity on leukemic cells, and has certain therapeutic effect on advanced stage CD19-positive B-cell acute lymphocytic leukemia patients who are repeatedly subjected to therapy such as radiotherapy, chemotherapy and symptomatic therapy by other drugs but cannot recover obviously.

The invention belongs to the technical field of biology and new medicines and discloses a chimeric antigen receptor (CAR) iRGD-scFv (G250)-CD8-CD28-CD137-CD3zeta and application thereof. The chimeric antigen receptor is formed by series connection of tumor penetrating peptide iRGD, a single-chain antibody of a humanized anti-human renal carcinoma antigen G250, a hinge region and a transmembrane region of CD8, and intracellular signal structural domains of CD28, CD137 and CD3zeta. The chimeric antigen receptor can be used for modifying T lymphocytes, and the modified T lymphocytes can be used for renal carcinoma treatment.

Provided is a pharmaceutical composition for preventing and treating chronic graft-versus-host disease (cGVHD) containing an anti-CD137 monoclonal antibody.The pharmaceutical composition containing the anti-CD137 monoclonal antibody as an active component reduces a cytokine produced from a CD4+ T cell, and increases a death of a donor CD4+ T cell, thereby effectively preventing and treating cGVHD, and thus can be useful for allogeneic stem cell transplantation.

The invention discloses a method for simultaneous and efficient amplification of CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells. The method comprises the steps as follows: the concentration of separated PBMC (peripheral blood mononuclear cells) is adjusted by a serum-free medium containing autologous plasma, an Anti-CD16 antibody, IL-2 and IL-15 are added, and then the mixture is transferred into a T175 culture flask for culture; an Anti-CD3 antibody and an Anti-CD137 antibody are added; a serum-free medium containing the autologous plasma, IL-2 and IL-15 is supplemented every two days according to the cell growth condition; the cell concentration is controlled to be about 1.5*10<6> / ml; and after culture is performed for 14-21 days, large quantities of high-purity CD<3+>CD<56+>CIK cells and CD<3->CD<56+>NK cells can be obtained simultaneously, and the total cell quantity can reach an effective value of the cell quantity required for adoptive cellular immunotherapy clinically for tumor. The method for simultaneous and efficient amplification of the CD<3+>CD<56+>CIK cells and the CD<3->CD<56+>NK cells is simple, convenient, effective and high in cell killing activity.

The present invention relates to the role of 4-1BB (CD137) ligand and anti-4-1BB (CD137) antibody in the treatment of cancers and diseases associated with 4-1BB (CD137) expression. More particularly, the present invention relates to the use of (i) 4-1BB (CD137) ligand for inducing proliferation and activation and promoting survival of B lymphocytes and (2) anti-4-1BB (anti-CD137) antibody for inhibiting proliferation and activation and inducing death of B lymphocytes.

The invention belongs to the field of immunology and particularly provides a method for amplifying and activating a natural killer cell (NK) in an oriented way under the mutual effect of a K562 cell, which is transfected by transmembranes IL-21, CD14, CD19, CD86 and CD137, and a low-concentration interleukin 2. According to the invention, the method comprises the following steps: transcribing expression carriers, which are used for stably expressing CD8 alpha-interleukin 21, CD14, CD19, CD86 and CD137, by using K562 cell lines, wherein the CD8 alpha is a membrane protein expressed on a cell membrane, and the interleukin 21 is expressed on the cell membrane to become a transmembrane protein after the CD8 alpha gene is connected with the interleukin 21 gene; and then culturing the K562 cell for a section of time; and finally, obtaining a purified K562 cell by using a physical and chemical method and then culturing the NK cell. According to the invention, by using the amplified and activated NK cell, the immunity of the patient can be enhanced, the viruses and bacteria are resisted, and high efficiency is obtained. The method for amplifying and activating the natural killer cell, provided by the invention, medically has wide purposes.

The present invention relates to method for depletion of CD137 positive cells using an anti-CD137 antibody-toxin complex, and more particularly, to a method for selective depletion of CD137 positive cells, comprising the step of contacting an anti-CD137 antibody-toxin complex with the CD137 positive cells. The method for selective depletion of CD137 positive cells in accordance with the present invention can be useful to prevent or treat various diseases including immune diseases mediated by the activation of the CD137 positive cells because this method is excellent in delivering a complex of an anti-CD137 antibody, specific to CD137 molecules, and a toxin to CD137 expressing cells and selectively killing the CD137 positive cells alone and is also excellent in suppressing cell proliferation.

The disclosure provides a chimeric antigen receptor (CAR) comprising a) an antigen binding domain of HA22, a transmembrane domain, and an intracellular T cell signaling domain; or b) an antigen binding domain of BL22, a transmembrane domain, and an intracellular T cell signaling domain comprising CD28 and / or CD137. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

The invention relates to an antibody or an antigen-binding fragment thereof that binds to a CD137 protein with a KD value of 1*10<-9> M or less. The antibody or the antigen-binding fragment thereof has strong specific recognition and binding ability to the CD137 protein, and can activate a NF-[kappa]B signaling pathway, promote the proliferation of PBMC cells and / or induce immune cells to secretecytokines. The invention also provides an application of the antibody or the antigen-binding fragment thereof in preparation of drugs for treatment or prevention of cancer or autoimmune diseases.

The invention belongs to the field of tumor biological products, and particularly relates to an chimeric antigen receptor, a gene of the chimeric antigen receptor, the recombinant expression vector ofthe chimeric antigen receptor, a CD22-CD19 double-targeting T cell and application of the T cell. The chimeric antigen receptor is CD22ScFv-L-CD19ScFv-CD8-CD137-CD3zeta and comprises CD22ScFv, connecting peptide L, CD19ScFv, a hinge region and a transmembrane region of CD8, an intracellular signal structural domain of CD137 and an intracellular signal structural domain of the CD3zeta which are connected in series. According to the chimeric antigen receptor, the gene of the chimeric antigen receptor, the recombinant expression vector of the chimeric antigen receptor, the CD22-CD19 double-targeting T cell and the application of the T cell, when B-cell line hematological malignant tumors are treated, the T cell modified by the chimeric antigen receptor not only can specifically recognize a tumor cell which is only expressed by a single target spot of a CD19 antigen or a CD22 antigen, but also can recognize tumor cells co-expressed by the two target spots of the CD19 antigen and the CD22antigen, compared with the single target spot CAR T, the double target spots CAR T have stronger anti-tumor activity, so that the immune escape of the tumor cells expressed by the low-abundance antigen is avoided, and therefore the recurrence risk is reduced.

The invention provides a preparation method of universal heterologous CAR-T cells and an application. Constructed CD28-CD137-CD19-CD3 full-length gene is introduced into allogeneic T cells of healthy persons with CRISPR / Cas9 technology, in order to produce CAR-T cells with targeting cytotoxicity; after amplification in vitro, the cells are fed back to patients for carrying out antineoplastic treatment, and in the treatment process, a PNAs method is used for removing lymphocyte in order to avoid antigraft reaction of hosts. The chimeric antigen receptors can be prepared in large scale with T lymphocyte of healthy human, and antineoplastic treatment of heterologous cancer patients.

The invention relates to a separation and efficient amplification culture method for an antigen specific T lymphocyte. By means of the immunomagnetic bead technology and the character of an active T cell expression CD137, the antigen specific T lymphocyte is separated from a complex cell mass; then an antigen specific T lymphocyte with high tumor killing activity is obtained through in-vitro efficient amplification culture. CD137L (CD137-ligand), IL-7, IL-15 and IL-2 are added in the culturing process, so that the phenomenon that activated and induced cells are liable to apoptosis in the culturing process is avoided, the amplification time is increased, and the killing activity of the antigen specific T lymphocyte is improved.

The invention relates to the field of immunology, in particular to a method for amplifying and activating a natural killer (NK) cell into a lymphokine-activated killer (LAK) cell by using a CD8 alpha-interleukin 21-CD137 compound. The method disclosed by the invention comprises the following steps of: forming the CD8 alpha-interleukin 21-CD137 compound by using CD8 alpha, interleukin 21 and a CD137 functional polypeptide, making an exogenous expression vector enter a host K562 cell, then activating a promoter and culturing a cell to obtain a cell for expressing a transmembrane interleukin 21-CD137 compound; and purifying the compound in the conventional way, and amplifying and activating a lymphocyte by using the purified compound to generate the LAK cell. The method has the advantage that: the LAK cell cultured and amplified by using the transmembrane interleukin 21-CD137 compound and a small dose of interleukin 2 is used for enhancing the immunity of a patient to help the patient resist tumors, viruses and bacteria. The method has a wide clinical using prospect.

The invention discloses an anti-CD20 chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector and an application. The anti-CD20 chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, CD20 VL, Optimal Linker C, a CD20 single-chain antibody heavy chain VH, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-CD20 chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.

The invention discloses an anti-EGFRvIII chimeric antigen receptor, an encoding gene, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. The anti-EGFRvIII chimeric antigen receptor comprises CD8 leader chimeric receptor signal peptide, an EGFRvIII single-chain antibody light chain VL, Optimal Linker C, an EGFRvIII single-chain antibody heavy chain VH, a CD8 Hinge chimeric receptor hinge, a CD8 Transmembrane chimeric receptor transmembrane domain, a CD137 chimeric receptor co-stimulated factor and a TCR chimeric receptor T cell activating domain which are connected in series. Moreover, the invention discloses an encoding gene of the anti-EGFRvIII chimeric antigen receptor, a recombinant expression vector, a construction method of the recombinant expression vector, and an application. Secretion of cell factors and an in-vitro killing effect of CAR-T cells are obviously improved, and the CAR-T cells have an outstanding clinical treatment effect.