32 results about "Adoptive immunotherapy" patented technology

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.

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.

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 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.

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.

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.

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

To provide 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.SOLUTION: The present invention provides a chimeric antigen receptor (CAR) protein, which binds to a specific antigen. For example, a CAR protein binding to FLDETLRSLA (SEQ ID NO: 2) and a CAR protein binding to YNPIRTTF (SEQ ID NO: 3) are illustrated.SELECTED DRAWING: Figure 6B

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 application provides a high-efficiency expansion culture method of umbilical cord blood gamma delta T cells and application thereof, and belongs to the technical field of biological medicine. Through a specific two-stage strategy of "initial induction culture + expansion culture", the application is simple in operation, stable in system, and high in success rate, effectively overcomes the defects of limited autologous blood source, unstable expansion and low cell activity in the prior art, and lays a foundation for large-scale preparation and allogeneic application of gamma delta T cells. The umbilical cord blood gamma delta T cells obtained by the method of the application are excellent in quantity, purity, activity and anti-tumor function, and have stronger tumor cell killing ability, and are especially suitable for adoptive immunotherapy. The application breaks through the technical bottleneck of the traditional culture system, provides a high-efficiency, stable and clinically convertible gamma delta T cell expansion scheme, and has important application prospect and market value.

The present invention relates to agents, compositions, and methods to confer and / or increase immune responses mediated by cellular immunotherapy.

Embodiments of the disclosure include methods and compositions in which NK cells are modified by the hand of man to express T-cell receptor and CD3 co-receptor on NK cells that do not naturally express them. Such modified NK cells work effectively with monospecific, bispecific or multi-specific antibodies, wherein the bispecific or multi-specific antibodies are tailored to comprise anti-CD3 antibodies that bind the modified NK cells, thereby triggering signaling, activation, and cytotoxicity of target cells to which the antibodies also bind. Thus, the NK cells are specifically configured to be able to work effectively with Bispecific NK cell engagers (BiKEs) as well as Bispecific T cell Engagers (BiTEs).

Provided herein are methods for preparing and characterizing SARS-cov2 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 calls 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 present invention relates to agents, compositions, and methods to confer and / or increase immune responses mediated by cellular immunotherapy.

To provide safer methods for modifying T cells, while generating T cells with maximal effector activity and functionality in vivo for T cell based adoptive immunotherapy, and modified T cells.SOLUTION: The disclosure provides a modified T cell and a method for preparing the same. The modified T cell comprises an exogenous nucleic acid encoding a T cell receptor (TCR) having affinity to an antigen on a target cell, and a nucleic acid encoding a bispecific antibody, where (a) the T cell expresses the TCR and the bispecific antibody on the surface of the T cell; (b) the bispecific antibody comprises a bispecific antigen binding domain, where the bispecific antigen binding domain comprises a first and a second single chain variable fragment (scFv) molecules; and (c) the first scFv molecule is specific for at least one antigen on a target cell, and the second scFv molecule is specific for an antigen on an activating T cell.SELECTED DRAWING: None

The invention provides a micro-environment dynamic regulation and control bioreactor for large-scale culture of immune cells. The micro-environment dynamic regulation and control bioreactor comprises a culture cavity, a temperature control assembly, a gas-liquid exchange assembly, a monitoring assembly and a PLC (Programmable Logic Controller), a sterile sampling port and an inoculation port are formed in the top of the culture cavity, a discharge port is formed in the bottom of the culture cavity, a bottom pipeline of the culture cavity is connected with a waste liquid collecting tank, and a microcarrier matrix and a stirring assembly are arranged in the culture cavity; the micro-environment dynamic regulation and control bioreactor further comprises a nutrition supply assembly. The micro-environment dynamic regulation and control bioreactor for the large-scale culture of the immune cells can dynamically regulate and control the culture micro-environment; meanwhile, a microenvironment dynamic regulation and control technology is matched, accurate matching of nutrition supply and microenvironment parameters is achieved, the NK / CIK cell in-vitro amplification multiple can be larger than or equal to 1000, the cell activity maintenance rate within 14 days is larger than or equal to 90%, the method can be used for tumor adoptive immunotherapy and large-scale production of immune cell preparations, and technical support is provided for industrialization of immune cell therapy products.

Described herein are biomimetic Janus particles useful as artificial antigen presenting cells capable of activating T cells in vitro. “Bull's eye” ligand patterns mimicking either the native or reverse organization of the T cell immunological synapse are provided on the surface of nano- or micro-sized particles. Methods for activating T cells in vitro using biomimetic Janus particles described herein are also provided. T cells activated by the biomimetic Janus particles can be used in adoptive immunotherapies for treating cancer, tolerance induction in autoimmune disease, autologous immune enhancement therapy, and viral infection immunotherapy. Also described herein are methods for producing a biomimetic Janus particle.

Embodiments of the present disclosure include methods and compositions in which NK cells are engineered to express an invariant NK T cell receptor and a CD3 co-receptor that are not naturally expressed on the NK cell. These engineered NK cells interact effectively with bispecific or multispecific antibodies engineered to include an anti-CD3 antibody that binds to the engineered NK cell, thereby inducing signaling, activation, and cytotoxicity of target cells that also bind the antibody. In this manner, the NK cells are specifically engineered to interact effectively with bispecific NK cell engagers (BiKEs) and bispecific T cell engagers (BiTEs).

Methods and compositions for use of tumor self-antigens in adoptive immunotherapy are disclosed herein, including search engines and algorithms for identifying tumor-specific immunotherapy targets. An example computer-implemented method can include receiving, by at least one processor, sequence data; identifying, by the at least one processor, one or more tumor-specific events associated with a plurality of molecular event classes from the sequence data; determining, by the at least one processor, a search space based on the one or more tumor-specific events; interrogating, by the at least one processor, a plurality of datasets based on the determined search space; and determining, by the at least one processor, one or more immunotherapy targets based on genetic aberrations from the sequence data.

The present disclosure relates to methods of treating cancer or preventing metastases of a cancer in a subject in need thereof. The disclosure further relates to compositions comprising a heterogeneous population of T cells with reactivity to individualized cancer epitopes, or neoantigens, that are useful for adoptive immunotherapy and methods for making such T cell compositions.

The present invention relates to isolated antibody fragments and more in particular single-domain antibodies that have affinity for tumor antigens and tumor-associated antigens such as HER2. Also provided herein is a pharmaceutical composition comprising the antibody fragment, the CAR immune cell comprising said fragment, or the nucleic acid or vector encoding said antibody fragment for use in the prevention and / or treatment of a tumor or cancer, or for use in adoptive immunotherapy such as CAR-T-cell therapy or targeted radiotherapy.

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.

To provide compositions and methods for immune cell modulation.SOLUTION: In one aspect, a composition comprises a population or subpopulation of immune cells, and one or more modulating agents selected from the group consisting of specific compounds. The one or more modulating agents (a) improve therapeutic potential of immune cells for adoptive cell therapy; (b) improve cell expansion, maintenance, and / or differentiation properties of immune cells; (c) improve cell proliferation, cytotoxicity, persistence, cytokine response and secretion, and / or cell recall responses of immune cells; and / or (d) increase the number or ratio of a desired immune cell subpopulation.SELECTED DRAWING: Figure 1A