206 results about "Cellular immunotherapy" patented technology

Genetically engineered, CE7-specific redirected immune cells expressing a cell surface protein having an extracellular domain comprising a receptor which is specific for CE7, an intracellular signaling domain, and a transmembrane domain, and methods of use for such cells for cellular immunotherapy of CE7+ neuroblastoma are disclosed. In one embodiment, the immune cell is a T cell and the cell surface protein is a single chain FvFc:ζ receptor where Fv designates the VH and VL chains of a single chain monoclonal antibody to CE7 linked by peptide, Fc represents a hinge —CH2—CH3 region of a human IgG1, and ζ represents the intracellular signaling domain of the zeta chain of human CD3. DNA constructs encoding a chimeric T-cell receptor and a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor are also disclosed.

The present invention relates to a genetically engineered, CD19-specific chimeric T cell receptor and to immune cells expressing the chimeric receptor The present invention also relates to the use of such cells for cellular immunotherapy of CD9+ malignancies and for abrogating any untoward B cell function. The chimeric receptor is a single chain scFvFc:ζ receptor where scFvFc designates the extracellular domain, scFv designates the VH and VL chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG1, and ζ represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain ζ are linked by a transmembrane domain such as the transmembrane domain of CD4. In one aspect, the chimeric receptor comprises amino acids 23-634 of SEQ I DNO:2. The present invention further relates to a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor.

The present invention relates to a composition for expanding lymphocytes comprising at least two types of cytokines selected from interleukin 2 (IL-2), interleukin 15 (IL-15) and interleukin 21 (IL-21). It further relates to a Method of preparing a population of clinically relevant lymphocytes, comprising the steps of: obtaining a body sample from a mammal in particular a tissue sample or body liquid sample, comprising at least one lymphocyte and optionally separating the cells in the body sample, culturing the body sample in-vitro to expand and / or stimulate lymphocytes in the sample wherein the culturing comprises using IL-2, IL-15 and / or IL-21, and optionally determining the presence of clinically relevant lymphocyte in the cultured sample. The present invention also relates to an immunotherapy and the population of clinically relevant lymphocytes.

The present invention provides methods and compositions to confer and / or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring genetically modified tumor specific CD8+ T cells in the presence of tumor-specific, subset specific genetically modified CD4+ T cells, wherein the CD4+ T cells confer and / or augment a CD8+ T cells ability to sustain anti-tumor reactivity and increase and / or maximize tumor-specific proliferation of the tumor-specific CD8+ T cells of interest. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and / or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

The invention discloses gRNA for knockout of a wild type T cell TCR [beta] strand and a method. The sequence of the gRNA is as shown in SEQ ID NO: 1, by utilizing a CRISPR / Cas9 technology, the gRNA and CRISPR / Cas9 jointly infect a T cell, the wild type T cell TCR [beta] strand is knocked out, and the T cell lacking the wild type TCR [beta] strand is constructed and used for CAR-T or TCR-T cellular immunotherapy. According to the gRNA for knockout of the wild type T cell TCR [beta] strand and the method, the knockout efficiency is high, the preparation method is relatively simple and easy, and T cells lacking wild type TCR [beta] strands can be provided for clinic rapidly and efficiently.

A method for enhancing anticancer capability of CIK cells is provided. The method includes knockout of a PD-1 gene of the CIK cells based on a CRISPR / Cas9 technique. The invention also provides enhanced type CIK cells obtained by the method. Experiments prove that the knockout of the PD-1 gene from the CIK cells can effectively enhance anti-hepatoma capability of the CIK cells, thus providing novel effector cells for tumor cellular immunotherapy.

The present invention provides a T-cell receptor (TCR) which binds to a peptide from the cytomegalovirus (CMV) phosphoprotein pp65 having the amino acid sequence NLVPMVATV (SEQ ID No. 1) when presented by a major histocompatability complex (MHC) molecule. The present invention also provides a nucleotide sequence encoding such a TCR, a vector comprising such a nucleotide sequence and its use to produce a CMV-specific T-cell. The present invention also provides the use of CMV-specific T-cell for cellular immunotherapy.

The invention discloses an expansion method of various lymphocyte subpopulations and application of the expansion method to preparation of an adoptive immunotherapy medicine for cancers. The expansion method comprises the following steps: S1, adding IFN gamma and zoledronic acid into a culture medium of PBMC collected in the blood of a tumor patient, and re-adding an OKT3 antibody and recombinant human interleukin-2 after culture to stimulate PBMC so as to finish preliminary expansion; S2, after finish of preliminary expansion, mixing immune lymphocytes with feeder layer cells, and after adding zoledronic acid, an OKT3 antibody and recombinant human interleukin-2, continually performing expansion. By adoption of the expansion method, after twice expansion, the sum of the immune cells can be 10,000 to 80,000 times by expansion, the expanded immune cells include alpha beta T cells, gamma delta T cells, NKT cells and NK cells, and tumor cells can be directly killed, or a cellular immunotherapy drug is prepared to kill the tumor cells.

The invention relates to the field of cellular immunotherapy of tumor and in particular to a medicine composition and application thereof. The medicine composition comprises a medicine specifically targeting kidney tumor GPC3, wherein the medicine specifically targeting kidney tumor GPC3 comprises any one or a combination of at least two of CAR-T (Chimeric Antigen Receptor T-Cell Immunotherapy) cells, an anti-GPC3 antibody, TCR-T (T-lymphocyte Cell Receptor) cells targeting GPC3, and siRNA of DC-CIK (Dendritic Cell-Cytokine-Induced Killer) cells targeting GPC3 or targeting silenced GPC3. Testsshow that GPC3 can be new targeting antigen of nephroblastoma, and by adopting the medicine composition, nephroblastoma can be effectively killed and inhibited.

The invention discloses an amplification method for an NK cell without trophocyte. The method comprises the following steps: adopting a blending culture solution for culturing the NK cell and culturing for 7 days, and then using a self-plasma culture medium for culturing, supplying the fluid per 2-3 days in the culturing process, maintaining the cell density of 2.0*106 / mL and culturing for more than 20 days. The blending culture solution is composed of 1-10% of self-plasma, 200-1500 IU / mL IL-2, 10-50ng / mL IL-15 and 10-50ng / mL IL-21 added into a lymphocyte culture medium. The self-plasma culture medium is composed of 1-10% of self-plasma and 200 IU / mL IL-2 added into a serum-free medium. According to the amplification method for the NK cell without trophocyte disclosed by the invention, cord blood or autologous peripheral blood is taken as a cell source, no trophocyte is required in the culturing process, the amplification efficiency is high and the purity of the acquired NK cell is high. The NK cell acquired according to the method can be used as a medicine compound for cell immunization therapy and is mainly used for treating and / or preventing infectious diseases and / or cancer.

A method for stimulating the immune system in immunocompromised patients in order to treat opportunistic infection. The method involves the infusion of intentionally mismatched allogeneic cells. In order to prevent graft vs. host disease complications, the allogeneic cells can be irradiated prior to infusion.

The invention discloses an antibody and a chimeric antigen receptor for targeting a BCMA protein, and a drug, and relates to the technical field of cellular immunotherapy. The antibody comprises a heavy chain CDR region represented by SEQ ID NO.22-24 and a light chain CDR region represented by SEQ ID NO.30-32, or comprises a heavy chain CDR region represented by SEQ ID NO.54-56 and a light chain CDR region represented by SEQ ID NO.62-64. The antibody has the ability to specifically bind to the BCMA protein, and the chimeric antigen receptor T cell prepared by using the antibody has a specifickilling effect on target cells positive for the BCMA protein, and can be used for preparing the drug for treating or preventing tumors.

The present invention relates to a composition for expanding lymphocytes comprising at least two types of cytokines selected from interleukin 2 (IL-2), interleukin 15 (IL-15) and interleukin 21 (IL-21). It further relates to a Method of preparing a population of clinically relevant lymphocytes, comprising the steps of: obtaining a body sample from a mammal in particular a tissue sample or body liquid sample, comprising at least one lymphocyte and optionally separating the cells in the body sample, culturing the body sample in-vitroto expand and / or stimulate lymphocytes in the sample wherein the culturing comprises using IL-2, IL-15 and / or IL-21, and optionally determining the presence of clinically relevant lymphocyte in the cultured sample.The present invention also relates to an immunotherapy and the population of clinically relevant lymphocytes.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

Provided herein are novel therapeutic compositions and methods that keep cellular immunotherapies in the circulation or at the site of injection for extended periods of time without resorting to the use of cytotoxic preconditioning. More specifically the compositions and methods herein lymphodeplete and reduce or ablate sites in the secondary lymphatics where the cellular immunotherapy is bound and sequestered, without the use of cytotoxic preconditioning.

The present invention relates to the field of cell immunotherapy and more particularly to a new generation of chimeric antigen receptors (CAR), allowing the control of immune cells endowed with such CARs through the interaction with small molecules. More particularly, the present invention relates to chimeric antigen receptor which comprise in at least one ectodomain a molecular switch turning the antigen binding function of the receptor from an off to on state, and vice versa. The present invention thus provides more controlled and potentially safer engineered CAR endowed immune cells, such as T-lymphocytes.

The invention relates to the field of cellular immunotherapy of tumors, in particular to a model and a method for detecting inhibiting effect of chimeric antigen receptor (CAR) T cells on hepatoma cells. The model is obtained by transplanting primary hepatoma tissues into a model living body, and transplanting the CAR T cells into the model living body. The model provided by the invention can be used for effectively simulating the tumor malignant degree of a patient, and assessing the inhibiting effect of the CAR T cells on hepatomas of different malignant degrees; the model can be used for effectively assessing the inhibiting effect of the expression of immunosuppression check point molecules in primary hepatoma cells on the CAR T cells.

Embodiments of the disclosure include compositions and methods useful for treating cancers that are sensitive to a chemotherapy, such as temozolomide. The methods allow effective cell immunotherapy to be used with chemotherapy when the cell immunotherapy is susceptible to being rendered ineffective by the chemotherapy. In specific aspects, the cancer is being treated by temozolomide (TMZ) and tumor antigen-specific T-cells that are resistant to TMZ.

The present invention provides HIDE1 as novel monocyte markers. Since HIDE1 are membrane proteins, monocytes can be specifically detected by using antibodies that bind to HIDE1. Further, HIDE1-positive monocytes can also be collected from peripheral blood or the like using a cell sorter, magnet, or such. Monocytes that can be prepared based on the present invention are useful in cell immunotherapy.

The invention discloses a BCMA antibody, a chimeric antigen receptor and a drug, and relates to the technical field of cellular immunotherapy. The BCMA antibody provided by the invention has a heavy chain CDR region shown in SEQ ID NO. 6-8 and a light chain CDR region shown in SEQ ID NO. 14-16, or has a heavy chain CDR region shown in SEQ ID NO. 38-40 and a light chain CDR region shown in SEQ ID NO. 46-48. The BCMA antibody has the ability to specifically bind a BCMA protein, and a chimeric antigen receptor T cell prepared by using the BCMA antibody has a specific killing effect on a target cell positive for the BCMA protein and can be used to prepare drugs for treating or preventing tumors.

The invention discloses a chimeric antibody and an immunocyte. The chimeric antibody provided by the invention has an amino acid sequence containing a target antibody, a transmembrane domain segment of a HLA-A2 (Human Leukocyte Antigen-A2) molecule and an intracellular domain segment of a CD3 compound protein zeta chain in sequence from a terminal N to a terminal C. The chimeric antibody can be expressed on the surfaces of any cells, when the chimeric antibody is expressed on the surface of an immunocyte, the immunocyte is endowed with a specific immunity by virtue of the target antibody on the chimeric antibody, and thus, the chimeric antibody provided by the invention can be specifically combined with a plurality of antigens along with different target antibodies in the chimeric antibody. The chimeric antibody, a single-domain antibody and an immunocyte for expressing the chimeric antibody, provided by the invention, are about to have broad application prospects in the cellular immunotherapy.

The invention belongs to the field of cellular immunotherapy and particularly relates to a CAR-T cytotoxicity indicating vector. The cytotoxicity indicating vector is a recombined lentiviral vector and is composed of an original lentiviral vector and an insertion sequence. The insertion sequence is composed of a tumor-correlation target antigen coding gene, a connection peptide coding gene and a luciferase coding gene from the 5' terminal to the 3'terminal in sequence. After CAR-T cells and CAR-T cytotoxicity indicating cells are mixed, a tumor-correlation target antigen expressed by the indicating cells can perform target guiding on CAR-T for combination, the indicating cells are split, and luciferase is released. Due to the fact that split cells are located in supernatant and the un-split cells are located in precipitate, the number of spit cells and the number of un-split cells can be worked out according to the relation between the indicating cell number and the luciferase activity value by detecting the activity value of luciferase in the supernatant and the activity value of luciferase in the precipitate, the proportion of the split cells is calculated, and the CAR-T cytotoxicity is indicated.

The invention discloses an application of gold platinum thermometal nano particles on preparation of cell immunotherapy accelerant. According to the application, the hydrogen peroxide enzymatic activity of the gold platinum thermometal nano particles is used, the gold platinum thermometal nano particles can react with hydrogen peroxide in the tumour hypoxia microenvironment and generate oxygen andhave good biocompatibility, the gold platinum thermometal nano particles are combined with cell immunotherapy and used as accelerant of cell immunotherapy, so that the tumour hypoxia situation is improved, inhibition of the tumour hypoxia environment to the killing capacity of the immune cell is lowered, accordingly, the killing effect of the immune cell to the hypoxia tumour cell is remarkably improved, and the gold platinum thermometal nano particles have wide application prospects on tumour immunotherapy.

The invention belongs to the technical field of cellular immunotherapy, and particularly relates to a PD-1 gene knockout MUC1-targeting CAR-T cell as well as a preparation method and application thereof. An MUC1-targeting chimeric antigen receptor is prepared firstly, wherein the MUC1-targeting chimeric antigen receptor comprises an antigen binding structural domain, a transmembrane structural domain, a co-stimulation structural domain and an intracellular signal transduction structural domain. Tn glycosylation MUC1 is used as a target spot, the target spot specificity is high, off-target is not likely to occur, and the safety of the CAR-T cells is improved. On the basis, the PD-1 gene knockout MUC1-targeting CAR-T cell is obtained, and after the PD-1 gene is knocked out and the CAR-T cell is transfused back into a body, the CAR-T cell failure and inactivation caused by PD-L1 expressed by tumors cannot occur, so that the efficient specific cell killing effect on tumor cells is achieved, and the curative effect of the CAR-T cell is improved.

The invention discloses the field of tumor cellular immunotherapy and particularly relates to a tumor cell vaccine which is modified by a PD-1 neutralizing antibody with combination of a GM-CSF factor and a preparation method thereof. In the invention, tumor cellular vaccine therapy is creatively combined with antibody therapy which relieves tumor immune-suppression, so that the prepared tumor cell vaccine simultaneously secreting the PD-1 neutralizing antibody and the GM-CSF factor can not only relieve the immune-suppression status of a tumor micro-environment but also enhance an antitumor immune reaction. The tumor cell vaccine is good in antitumor treatment effect, is excellent in development value and provides a new approach of tumor cellular immunotherapy.