43 results about "Adoptive immunity" patented technology

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.

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 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.

The present invention relates to the field of adoptive immune cell therapy, in particular adoptive T cell therapy. The present invention provides a conversion receptor which is capable of effectively converting an immunosuppressive signal of TGF [beta], which is normally present in the hostile tumor environment of a solid tumor, into a co-stimulatory signal, thereby improving T cell activation, and which can be safely used in therapy. Also provided are nucleic acids encoding the transforming receptors, cells expressing the receptors and pharmaceutical compositions comprising the cells, in particular for the treatment of cancer or infectious diseases, such as adoptive T cell therapy by solid tumors.

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

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.

The invention provides a fusion protein for enhancing adoptive immune curative effect and application thereof. Specifically, the invention provides a fusion protein composed of a PD1 extracellular element or a TGF-beta extracellular element, a PD1 transmembrane segment or a TLR transmembrane segment, and a TLR intracellular segment. The fusion protein provided by the invention can convert an inhibitory signal of a tumor immune microenvironment into an activation signal, thereby promoting immune cell proliferation and enhancing the ability of immune cells to kill tumor cells. The invention also provides an engineered immune cell for simultaneously expressing the fusion protein and the chimeric antigen receptor, a preparation method of the engineered immune cell and the like.

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 present invention relates to the technical field of biomedicine, and specifically relates to immune cells targeting EpCAM and a medical use thereof. Provided is a use of immune cells in the preparation of a drug for preventing or treating a tumor; the immune cells are cells for adoptive immune cell therapy, which can target and kill EpCAM-expressing cells; and the tumor expresses EpCAM and is a metastatic tumor.

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 is directed to humanized CD37-CAR comprising humanized CD37 scFv of the present invention. The present invention is also directed to a bispecific CD19-humanized CD37 CAR, comprising: (i) CD19 VL, (ii) Humanized CD37 ScFv, (iii) CD19 VH, (iv) a transmembrane domain, (v) at least one co-stimulatory domains, and (vi) an activating domain. The CARs of the present invention are useful in the field of adoptive immunity gene therapy for hematological cancers.

The invention relates to the field of biological medicines, in particular to a TCR55 mutant and application thereof.The TCR55 mutant comprises an alpha chain and a beta chain, the TCR55 mutant is obtained after mutation is conducted on the basis of wild TCR55, and the alpha chain of the TCR55 mutant is a mutant obtained after any one of the following sites on the alpha chain of the wild TCR55 is mutated into histidine, the fourth position D and / or the fifth position E of the CDR2 alpha, and the seventh position A of the CDR3 alpha; or the beta chain of the TCR55 mutant is a mutant obtained by mutating any one of the following on the beta chain of the wild type TCR55 into histidine: the second site N of CDR1beta, the second site A of CDR2beta, the fourth site E and / or the sixth site T of CDR2beta, and the thirteenth site Y of CDR3beta. The mutant can be used for identifying HIV (Pol448-456) / HLA-B35, has high activating power, triggers downstream signal transduction, and can be used for transforming T cells to form specific high-activating-power TCR-T cells for T cell adoptive 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.

This invention relates to the short-chain fatty acid pentanoate and its use as enhancer for cellular immune therapy and anti-tumor therapy. The present invention specifically relates to the metabolite pentanoate and its use in the production of antigen-specific or genetically engineered immune cells. The invention also relates to pharmaceutical compositions comprising such immune cells, as well as their uses in cellular immune therapy (adoptive immune therapy), in particular to an improvement in the treatment of cancer, infectious diseases and immune cell-mediated diseases by means of cellular immune therapy.

Adoptive immunotherapy using T cells genetically redirected via expression of a chimeric antigen receptor (CAR) is a promising approach for cancer treatment. However, this immunotherapy partly depends on the optimal molecular design of the CAR, which involves an extracellular ligand-binding domain linked to an intracellular signaling domain via a spacer and / or transmembrane sequence.

The invention discloses a method for enhancing the immune function of dendritic cells by using 11-site single ubiquitin molecules, and relates to the technical field of gene engineering. The invention discloses a 11-site single ubiquitin molecule which is a ubiquitin molecule only retaining 11-site lysine, and relates to the technical field of gene engineering. Dendritic cells are separated from mouse bone marrow, the bone marrow-derived dendritic cells are pretreated with 11-site single ubiquitin molecules, then in-vitro adoptive immunization is performed, and finally an enzyme-linked immunosorbent assay spot experiment and a flow cytometry experiment are performed. Experiments prove that the antigen-specific CTL (cytotoxic T lymphocyte) inducing capacity of the treated dendritic cells is enhanced; the 11-site single ubiquitin molecule can enhance the phagocytic ability of the dendritic cells to the antigen and the ability of the dendritic cells to transvey lymphocytes in the receptor to generate perforin and granzyme B; the mechanism of the 11-site single ubiquitin molecule for enhancing the presentation and immune function of the dendritic cells on the antigen is mainly realized by a proteasome degradation pathway.

Disclosed is a recombinant T cell receptor that recognizes the KMT2A: :AFF1 fusion neoantigen presented by HLA- DPAl*02 : 01 DPBl*01 : 01, polynucleotides encoding the recombinant T cell receptor, and an expression vector and recombinant host cell comprising such polynucleotides. A method of using the recombinant T cell receptor in adoptive immunotherapy for treating leukemia is also provided.

The invention discloses a method for reducing the immune function of dendritic cells by using 27-site single ubiquitin molecules, and relates to the technical field of gene engineering. The 27-site single ubiquitin molecule is a ubiquitin molecule only retaining 27-site lysine, dendritic cells are separated from mouse bone marrow, the bone marrow-derived dendritic cells are pretreated with the 27-site single ubiquitin molecule, then in-vitro adoptive immunization is carried out, and finally an enzyme-linked immunosorbent assay spot experiment and a flow cytometry experiment are carried out. Experiments prove that the antigen presenting capability of the treated dendritic cells is obviously reduced, and the antigen-specific CTL inducing capability of the treated dendritic cells is also reduced; the 27-site single ubiquitin molecule can reduce the capability of generating IFN-gamma, perforin and granzyme B by lymphocytes in a dendritic cell transfer receptor. The 27-site single ubiquitin molecule inhibits splenocytes of a transfer receptor to generate perforin and granzyme B through a lysosome way.

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.

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.