78 results about "Adoptive immunotherapy" patented technology

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified nave, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naïve, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

Provided herein are methods for preparing and characterizing SARS-co2 antigen specific immune cell cultures and preparations and methods of using the same in adoptive immunotherapy for cancer, infections and immune disorders. Also, provided are compositions and methods for generating immune cells expressing synthetic antigen binding receptors targeting SARS-cov2 and methods of use of these cells for the treatment and prevention of COVID-19. Also provided are compositions and methods for determining immune response to SARs-cov2 in a subject, detecting SARS-cov2, measuring cytotoxicity induced by SARS-cov2, and detecting the expression and cytotoxicity of synthetic antigen binding receptors targeting SARS-cov2.

The invention relates to antibodies or fragments thereof directed against HBV and uses thereof, such as their use in adoptive immunotherapy, and treating HBV infection or associated diseases.

The invention relates to an engineered immune cell for overexpressing integrin as well as preparation and application of the engineered immune cell. The engineered immune cell expresses integrin beta1 or integrin beta3. The expression of the integrin beta1 or the integrin beta3 can improve the in-vitro migration ability of the T cells, enhance the in-vitro tumor killing ability of the T cells, improve the in-vivo anti-tumor ability of the T cells and improve the infiltration proportion in T cell tumors. The T cell overexpressing the integrin beta1 or the integrin beta3 provided by the invention can enhance the infiltration capacity of the T cell and improve the effector function of the T cell so as to promote the anti-tumor capacity of the T cell, and is suitable for clinical treatment of any adoptive immunotherapy, including clinical treatment of tumors, infection and autoimmune diseases.

Intracellular delivery of a genetic construct to immune cells including: obtaining a deterministic mechanoporation (DMP) platform that includes a substrate having a surface and a plurality of capture sites, each said capture site having a boundary shape at the surface adapted and configured to support thereon a cell, and each said capture site having a bottom and including a sub-micron-scale projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and / or wall of the cell, and wherein the substrate has a plurality of aspiration vias situated at the bottom of the capture sites; introducing the cells to the surface in a liquid media; capturing the cells within the capture sites by applying a first hydrodynamic force; applying a second hydrodynamic force on the captured cell and locally rupturing the membrane and / or wall of the cell with the projection, introducing the genetic construct into the cells, and releasing the porated cells from the capture sites. Also disclosed are methods of chimeric antigen receptor (CAR) T cell adoptive immunotherapy and T cell receptor (TCR) therapy.

The present invention relates to methods for developing engineered T-cells for immunotherapy that are both non-alloreactive and resistant to immunosuppressive drugs. The present invention relates to methods for modifying T-cells by inactivating both genes encoding target for an immunosuppressive agent and T-cell receptor, in particular genes encoding CD52 and TCR. This method involves the use of specific rare cutting endonucleases, in particular TALE-nucleases (TAL effector endonuclease) and polynucleotides encoding such polypeptides, to precisely target a selection of key genes in T-cells, which are available from donors or from culture of primary cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

The invention relates to an inducible chimeric co-stimulatory receptor (CCR) comprising an intracellular T cell activation dependent localization domain. The invention further relates to an immune cell expressing the inducible CCR, a nucleic acid molecule encoding said inducible CCR, and to a pharmaceutical composition, comprising said immune cell or said nucleic acid molecule. The invention further relates to a method of producing said immune cell and to a method of treating a malignancy, comprising providing immune cells expressing the inducible CCR to a patient in need thereof.

The present invention refers to a novel and efficient method for large-scale selective generation of yδ T cells, preferably human Vδ1+yδ T cells, optimal for clinical application in adoptive immunotherapy of cancer. In this sense, considering that both human cord blood HPCs, currently elected as source of stem cells in the clinic, and human early thymic progenitors can efficiently generate de novo human yδ T cells in response to Notch signalling, and most efficiently in response to the Notch ligand Jag2, the method thus comprises inducing the differentiation of cord blood CD34+ hematopoietic progenitor cells (HPCs) and / or human CD34+ early thymic progenitors, by activating them with Jag2 Notch ligands.

The invention relates to the technical field of adoptive immunotherapy, in particular to a double-target CD19 / CD79b CAR structure and application thereof. The structure comprises a Loop CAR structure or a tan CAR structure, and the Loop CAR structure or the tan CAR structure comprises a signal peptide sequence, an antigen binding structural domain, a connecting peptide, an antigen binding structural domain, a hinge region, a transmembrane structural domain, a costimulatory signal molecule and a cytoplasm signal transduction sequence which are connected in sequence; the antigen binding structural domain is an independent scFV structure aiming at specific targets, and the specific targets comprise CD19 and CD79b. The structure can be applied to immune cells, nucleic acid molecules and carriers. The structure can improve the killing effect.

A modified human cytotoxic lymphocyte cell is provided for adoptive immunotherapy, comprising an inactivating mutation in SMAD4 gene, which renders the cell resistant to the immunosuppressive effects of TGF-β and allows it to maintain its cytotoxicity. Additionally, a cell population and a pharmaceutical composition comprising the modified human cytotoxic lymphocyte cell are also provided, which are useful in the treatment of cancer. Particularly, it is provided modified NK cells for an off- the-shelf treatment.

The invention relates to the technical field of biotechnology and immunotherapy, and discloses a method for inducing and amplifying pMHC specific homologous TSCM, which comprises the following steps: a) preparing pMHC presenting a single antigen peptide; b) sorting lymphocytes and mononuclear cells from a donor, and connecting the pMHC presenting the single antigen peptide obtained in the step a) to the surface of the separated mononuclear cells as stimulating cells; c) co-culturing the sorted lymphocytes serving as effector cells and stimulated cells in a culture medium containing a glycogen synthase kinase-3beta inhibitor, and inducing to generate pMHC specific homogeneous TSCM; and d) separating the pMHC specific homologous TSCM obtained in the step c). The method can induce and amplify sufficient pMHC specific homogeneous TSCM for adoptive immunotherapy, overcomes self tolerance and avoids or alleviates GVHD (Growth Vitamin Horse Disease); the preparation method is simple, induction and amplification efficiency is high, and universality and flexibility are achieved.

The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and / or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) “off-the-shelf” T cells for administration to multiple recipients, eventually across immunogenic barriers, and / or 4) cytotoxic potential and anti-tumor activity.

The present disclosure provides methods and compositions for immunotherapy employing a modified T cell or NK cell comprising a receptor that binds to newly identified tumor antigens that can be administered to patients for disease (e.g., cancer) treatment. Also described are polynucleotides and vectors encoding the same.

The invention relates to the technical field of cellular immunotherapy, in particular to an antigen epitope peptide of a CD40 ligand, an antibody and application. The CD40LG target is mainly expressed by CD4 + T cells, so that self-killing is greatly reduced. In addition, as a novel target, the CD40LG can effectively improve tumor immune escape. The antibody provided by the invention can specifically recognize CD40LG, and has good affinity. The compound can be used for constructing cells or ADC drugs for adoptive immunotherapy.

Disclosed herein is a method for enhancing adoptively transferred autologous or allogeneic immune effector T-cells (including gamma delta T cells (γδ-T cells)) by targeting the thioredoxin (TRX)-interacting protein (TXNIP). In addition, disclosed herein are cDNA sequences for the co-expression of immune receptors (CARs, TCRs, etc) in combination with guide RNAs, and / or artificial or natural microRNAs, and / or shRNAs targeting TXNIP.

The present disclosure relates to methods of treating cancer or preventing metastasis of cancer in a subject in need thereof. The disclosure further relates to compositions comprising heterogeneous populations of T cells reactive to individualized cancer epitopes or neoantigens useful for adoptive immunotherapy, as well as methods for preparing such T cell compositions.

The invention provides a cascade response self-assembly polypeptide for remodeling tumor cell antigen composition, a bioactive solution of the cascade response self-assembly polypeptide and application of the cascade response self-assembly polypeptide. The polypeptide sequentially comprises a hydrophobic end-capping group, an alkaline phosphatase response self-assembly polypeptide sequence, a reduced glutathione response sequence and a T cell epitope peptide sequence. The polypeptide can respond to high-expression alkaline phosphatase in a tumor microenvironment to generate self-assembly and promote efficient internalization of cells; then, the antigen peptide is released under the action of reductive glutathione in tumor cells, and the antigen complex is given to the tumor cells through a main histocompatibility complex I-type molecular antigen presentation pathway. In addition, the specific hydrophobic end-capping group can up-regulate expression of I-type molecules of main histocompatibility complexes of tumor cells, enhance antigen presentation and remarkably enhance the recognition and killing efficiency of antigen-specific T cells on the tumor cells. Combined adoptive immunity and immune checkpoint inhibitor therapy is suitable for combined immunotherapy of solid tumors.

This invention relates to the use of "off-the-shelf" allogeneic therapeutic cells in combination with chemotherapy for the treatment of cancer patients. In particular, the inventors have developed a method for engineering allogeneic T-cells resistant to chemotherapy agents. The therapeutic benefits provided by this strategy should be enhanced through the synergistic effect between chemotherapy and immunotherapy. Specifically, this invention relates to a method for modifying T-cells by inactivating at least one gene encoding a T-cell receptor component and by modifying said T-cells to confer drug resistance. This invention opens the door to standard and affordable adoptive immunotherapy strategies for treating cancer.

To provide an improved composition for adoptive T cell therapy for treating, preventing or ameliorating at least one symptom of cancer, infectious disease, autoimmune disease, inflammatory disease and immune deficiency, or conditions associated therewith.SOLUTION: The present disclosure relates generally, in part, to an improved adoptive immunotherapy and, in certain embodiments, to an immune effector cell, chimeric TGFβ receptor (CTBR), and composition, which comprise an αβTCR that binds to MAGEA4, preferably a human pairing-enhanced αβTCR that binds to MAGEA4, preferably a polynucleotide encoding the MAGEA4 peptide GVYDGREHTV (SEQ ID NO: 1) presented by an HLA-A*02:01 encoded molecule, as well as to methods of using the same.SELECTED DRAWING: None

Embodiments of the present disclosure include methods and compositions for modifying NK cells by a human hand to express a T cell receptor and a CD3 coreceptor on NK cells that are not naturally expressed. Such modified NK cells act effectively with a monospecific antibody, a bispecific antibody, or a multispecific antibody, and the bispecific antibody or multispecific antibody is adjusted to consist of an anti-CD3 antibody that binds to the modified NK cells, thereby inducing signal transduction, activation, and cytotoxicity of target cells to which the antibody also binds. Thus, NK cells are specially configured to be able to act effectively with bispecific NK cell engagers (BiKEs) and bispecific T cell engagers (BiTEs).

Sotorasib augments the KRAS-G12C mutant cancer cells response to TNFα by Increasing TNFR1 surface expression, which in turn upregulates TNFα and IFNy down-stream target genes and ultimately enhances cancer cell death. In TACE-dependent mechanism, Sotorasib inhibited TNFR1 shedding off the KRAS-G12C mutant cancer cells. Additionally, Sotorasib significantly promotes the expansion of tumor infiltrating lymphocytes (TILs). In, addition, it generates a “hot” tumor microenvironment with strikingly augmented T cell effector phenotype. These results suggest that sotorasib regulation of TNFa and IFNy plays a crucial role in generating a more immune active tumor microenvironment. Consistently, sotorasib combined with CAR-T adoptive cell transfer and anti-PD1 treatment enhanced their anti-tumor effect. Therefore, disclosed herein is a method for treating KRAS-G12C mutant cancer in a subject, the method involving adoptively transferring an effective amount of autologous or allogeneic immune effector cells (T cells) to the subject in combination with a KRAS-G12C inhibitor

The application belongs to the technical field of biotechnology, and particularly relates to a staged precise regulation in vitro expansion culture method of high-activity gamma delta T cells. In the synergistic activation stage, the complex activator containing zoledronic acid, IL-2, IL-15, IL-12 and IL-21 is used to significantly improve the early activation level of the gamma delta T cells; in the dynamic expansion stage, the concentration of metformin is adjusted step by step to support the continuous and efficient proliferation of the cells; in the gradient maturation stage, the combination system of N-acetyl cysteine, TWS119 and DL-alpha tocopheryl acetate is introduced to help maintain the functional activity and antioxidant state of the cells in the later culture stage. The gamma delta T cells with a purity higher than 90% and an expansion multiple more than 100 times can be obtained by using the method to culture for 10 days, and the cells exhibit significant killing activity to tumor cells, are suitable for the adoptive immunotherapy of tumor and infectious diseases, and have good clinical application prospects.

Embodiments of the disclosure encompass adoptive immunotherapy related to cells expressing multiple chimeric antigen receptors (CARs). In specific embodiments, T cells express a HER2-specific CAR, an IL13Rα2-specific CAR, and an EphA2-specific CAR. In particular embodiments, the cells are utilized for cancer treatment, including for glioblastoma.

The present disclosure provides compositions and methods for stimulating, enriching, expanding, and / or activating engineered cells that express a recombinant receptor, e.g., a chimeric antigen receptor. In some embodiments, the provided methods include ex vivo or in vitro stimulation, enrichment, expansion, and / or activation of cells by incubation with a particle, e.g., a bead particle, attached to a binding molecule, such as a polypeptide antigen or anti-idiotype antibody, that recognizes or binds to the recombinant receptor. Also provided herein are methods for transfecting or transducing cells that have not been previously incubated with an activating or stimulating agent, such as have not been incubated with anti-CD3 / anti-CD28 antibodies and / or one or more recombinant cytokines, by transducing or transfecting the cells in the presence of the particles with attached binding molecules. In some embodiments, the provided compositions can be used in methods to prepare cells, e.g., genetically engineered T cells, for of adoptive immunotherapy.

The present invention relates to a novel and efficient method for the large-scale selective generation of γδ T cells, preferably human V51+ γδ T cells, optimal for clinical application in adoptive immunotherapy against cancer. In this regard, taking into account that both human cord blood HPCs and human early thymic progenitor cells, the current source of stem cells of choice in the clinic, can efficiently generate de novo human γδ T cells in response to Notch signaling, most efficiently in response to the Notch ligand Jag2, the method comprises inducing the differentiation of cord blood CD34+ hematopoietic progenitor cells (HPCs) and / or human CD34+ early thymic progenitor cells by activating these progenitors with the Jag2 Notch ligand.

Provided herein is the use of a first population of allogeneic T-cells recognizing a first EBV epitope, and a second allogenic population recognizing a second EBV epitope in the treatment of EBV-associated disorders. Also disclosed is the use of a population of allogeneic T-cells recognizing an EBV antigen in combination with a further therapeutic agent such as an immunotherapeutic agent, a MAPK, BET or MEK pathway inhibitor for treating EBV-associated disease.

A method of expanding TCRalpha deficient T-cells by expressing pTalpha or functional variants thereof into said cells, thereby restoring a functional CD3 complex. This method is particularly useful to enhance the efficiency of immunotherapy using primary T-cells from donors. This method involves the use of pTalpha or functional variants thereof and polynucleotides encoding such polypeptides to expand TCRalpha deficient T-cells. Such engineered cells can be obtained by using specific rare-cutting endonuclease, preferably TALE-nucleases. The use of Chimeric Antigen Receptor (CAR), especially multi-chain CAR, in such engineered cells to target malignant or infected cells. The invention opens the way to standard and affordable adoptive immunotherapy strategies for treating cancer and viral infections.

The invention discloses a method for improving proliferation and activity of cytokine-induced killer cells, and belongs to the technical field of cellular immunity. According to the method, the human peripheral blood mononuclear cells are firstly cultured in the culture medium containing the cell factors, then the obtained CIK cells are cultured in the culture medium containing the cell factors and the PP2A inhibitor, the amplification efficiency of the CIK cells is improved through the PP2A inhibitor, and the proportion of CD3 + CD56 + cells in the CIK cells is increased; according to the invention, a cell signal transduction pathway regulator PP2A inhibitor is ingeniously introduced, and culture conditions are optimized, so that the amplification efficiency of CIK cells is remarkably improved, and the proportion of functional subgroups is improved. Meanwhile, on the basis of improving the cell performance, the preparation cost of the CIK cell is relatively reduced, and the CIK cell is particularly suitable for preparing a CIK cell preparation required by adoptive immunotherapy and can be widely applied to treatment of solid tumors and blood system tumors.