155 results about "Central Memory T-Cell" patented technology

The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. 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 present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

The invention discloses a composition capable of stimulating expansion of T cells. Active factors of the composition comprise an Anti-CD3 antibody, an Anti-CD28 antibody, IL-2, IL-7 and IL-21. Through an HIV-1 specificity polypeptide combination and a multiple cell factor combination, in-vitro expansion of the antigen-specific memory T cells (TSCM and TCM) of an HIV-1 infected person can be effectively and continuously stimulated, and meanwhile the proportion of the expanded CD8<+> memory T cells, especially the CD8<+> TSCM is increased. The half-life period of adoptive immunotherapy reinjection cells can be prolonged, therefore, the immune surveillance achieving ageing of the adoptive immunotherapy reinjection cells is prolonged, and the potential of controlling HIV-1 latent infection for a long term is achieved. According to the method, the advantages that operation is simple, and materials are easy to obtain are achieved, and good technical support is supplied to wide development of anti-infection adoptive immunotherapy.

The invention relates to an antigen and TLR agonist targeting co-loaded cationic phospholipid-polymer hybrid nanoparticle vaccine adjuvant, and a preparation method and an application thereof. A hydrophobic inner core is encapsulated with a TLR7 agonist, a phospholipid layer is encapsulated with a TLR4 agonist, an antigen is adsorbed by cationic phospholipids in the phospholipid layer, and ligation of a mannose ligand makes the vaccine adjuvant like a specific targeting antigen to have the dendritic cell presenting ability, so the DC cell intake and the maturation promoting effect are enhanced; and the antigen is protected by hybridized nanoparticles, the antigen uptake by DC cells is improved, immune response after antigen stimulation is significantly enhanced by the TLR agonist, and thecross-presentation of the antigen is significantly improved, so vaccine adjuvant has a strong potent T cell killing effect, can induce cytokine secretion, has a long-acting memory T cell response, andhas an excellent prevention effect on tumors.

The present invention relates generally to methods for stimulating T cells, and more particularly, to methods to eliminate undesired (e.g., autoreactive, alloreactive, pathogenic) subpopulations of T cells from a mixed population of T cells, thereby restoring the normal immune repertoire of said T cells. The present invention also relates to compositions of cells, including stimulated T cells having restored immune repertoire and uses thereof.

The present invention provides a method for enhancing the immune function of a memory T cell which comprises the step of coinhibting signalling via an inhibitory receptor which regulates T cell exhaustion and via the p38 MAP kinase signalling pathway in the T cell, and a method for treating and / or preventing an immune condition in a subject, which comprises the step of enhancing the immune function of a memory T cell in the subject by such a method. There is also provided a pharmaceutical composition or kit comprising an agent capable of inhibiting signalling via an inhibitory receptor which regulates T cell exhaustion, such as PD-1, and an agent capable of inhibiting the p38 MAP kinase signalling pathway.

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 under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

A method of treating a disease in a subject in need thereof is disclosed. The method comprising: (a) transplanting a non-syngeneic cell or tissue graft to the subject; and (b) administering to the subject a therapeutically effective amount of an isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, and further wherein the cells are either: (i) non-syngeneic with both the subject and the graft; or (ii) non-syngeneic with the graft and syngeneic with the subject, thereby treating the subject.

The present invention is directed to a method for promoting function, activation and proliferation of T helper lymphocytes such as those that express IL17 and IL22 (Th-IL17+ and Th-IL22+ T cells). The method features isolating a population of T cells from a subject such as a human and incubating the population of T cells in a serum-free culture medium that contains one or more cytokine. The T cells may be memory T cells (TM) such as, for example, CCR6+CD45RO+ memory T cells (TM), and the one or more cytokine may be, for instance, one or more of IL-2, IL-7 and IL-15. Likewise, the invention provides a method for expanding an activated population of T helper lymphocytes by the same means.

The present invention provides a composition comprising a chimeric polypeptide comprising a recall antigen that reactivates memory T cells in a subject and a new antigen that activates naïve B cells in a subject and a composition comprising a nucleic acid encoding a chimeric polypeptide comprising a recall antigen that reactivates memory T cells in a subject and a new antigen that activates naïve B cells in a subject. Further provided are methods of modulating an immune response, as well as treating and / or preventing disease in subjects in whom the ability to mount an immune response to a new antigen is impaired, by administering the compositions of this invention.

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 belongs to the field of cell culture, particularly relates to a method for in-vitro culture and enrichment of CD8+ T cells, and more particularly relates to a method for directional amplification of a large amount of CD8+ T cells in peripheral blood mononuclear cells of a human body by using an irritant. The T cells obtained by the technical scheme are large in proliferation number and high in activity; the ratio of the CD8+ T cells to CD4+ T cells can be increased to 2-5 : 1 from about 1 : 2 in a normal physiological status; and in a target culture, the content of central memory T cells exceeds 30% based on the total cell number.

The invention relates to a construction method of a human stem memory T cell bank. The method comprises the following steps of human peripheral blood collection, peripheral blood mononuclear cell separation, initial T cell sorting, stem memory T cell preparation, cell cryopreservation and coding and storage. According to the construction method of the human stem memory T cell bank, a method of conducting directionally inducing in vitro is adopted, enough stem memory T cells (TSCM) can be obtained in a short time and subjected to bank construction, the volume of needed peripheral blood is small, and the construction method of the human stem memory T cell bank has the advantages of being low in cost, low in requirement on lab condition, easy to operate and the like.

A method of treating a disease in a subject in need thereof is disclosed. The method comprising: (a) transplanting a non-syngeneic cell or tissue graft to the subject; and (b) administering to the subject a therapeutically effective amount of an isolated population of cells comprising non-graft versus host (GVHD) inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation, and further wherein the cells are either: (i) non-syngeneic with both the subject and the graft; or (ii) non-syngeneic with the graft and syngeneic with the subject, thereby treating the subject.

An isolated population of cells comprising non-GVHD inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype is provided. The cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation. Methods of generating same, use of same and methods of treatment are also provided.

A method of generating an isolated population of cells comprising anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance-inducing cells and / or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) contacting peripheral blood mononuclear cells (PBMC) with a third party antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (b) culturing the cells resulting from step (a) in the presence of IL-21, IL-15 and IL-7 in an antigen free environment so as to allow proliferation of cells comprising the central memory T-lymphocyte (Tcm) phenotype.

The invention discloses a chimeric antigen receptor targeting human GPC3, the chimeric antigen receptor comprises an extracellular antigen binding region, a transmembrane region and an intracellular signal structural domain which are sequentially connected in series, the extracellular antigen binding region is combined with a GPC3 antigen, the extracellular antigen binding region comprises anti-GPC3 scFv used for combining the GPC3 antigen, wherein a heavy chain amino acid sequence is shown as SEQ ID NO. 1, and a light chain amino acid sequence is shown as SEQ ID NO. 2. Compared with the priorart, the chimeric antigen receptor is constructed by taking the human GPC3 as a target spot, and particularly, amino acids in ITAM2 and ITAM3 regions of CD3zeta are mutated, so that constructed T cells modified by the chimeric antigen receptor have stronger killing activity on tumor cells; moreover, more central memory T cells are provided, GPC3 positive tumor cells are killed in a targeted manner, the tumor recurrence rate after treatment is effectively reduced, and the life cycle of a patient is prolonged.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is disclosed. Methods of generating same and using same are also disclosed.

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.

An isolated population of cells comprising non-GVHD inducing anti-third party cells having a central memory T-lymphocyte (Tcm) phenotype is provided. The cells being tolerance-inducing cells and capable of homing to the lymph nodes following transplantation. Methods of generating same, use of same and methods of treatment are also provided.

Conventional cancer immunotherapy falls short at efficiently expanding T cells that specifically target cancerous cells in numbers sufficient to significantly reduce the tumor size or cancerous cell number in vivo. To overcome this limitation, provided herein are nanoparticles coated with MHC class I and / or class II molecules presenting tumor-specific antigens and co-stimulatory molecules and their use to expand antigen-specific anti-tumorigenic T cellsto levels not achieved in current immunotherapeutic techniques. These antigen-specific anti-tumorigenic T cells include cytotoxic T cells, effector T cells, memory T cells, and helper T cells that are necessary to initiate and maintain a substantial immune response against metastatic or non- metastatic cancerous, pre-cancerous, or neoplastic cells in vivo.; The present invention describes a systemic approach to targeting cancerous or pre-cancerous cells that are circulating cells, as in lymphomas, migratory metastatic cells, and solid tumors.

The invention is directed to compositions and methods for generating or enhancing the immune system of a patient against infection by a pathogen, and in particular MTB. Compositions of the invention contain one or more non-naturally occurring antigens that generate an effective cellular or humoral immune response to MTB and / or antibodies that are specifically reactive to mycolic acid or to the surface of MTB. The greater activity of the immune system generated by a vaccine of the invention involve an conjugation of peptides to increase in the generation of memory T cells that provide for a greater and / or longer lived or extended response to an MTB infection. Preferably a response involves an increased generation of antibodies that enhance immunity against MTB infection and promote an enhanced phagocytic response.

The present invention provides a method for efficiently preparing memory T cells by combining TWS119 and cytokines IL-7 and IL-21. The method includes collecting human peripheral blood; performing density gradient centrifugation to obtain human peripheral blood mononuclear cells; sorting CD8<+>T cells with a magnetic separation sorter; adding the CD8<+>T cells into a medium containing a stimulantCD3 / CD28 conjugated magnetic beads, cytokines IL-7and IL-21 and TWS119; and performing amplification so that a high number of CD8<+>T cells having Tcm and Tscm phenotypes can be obtained in the seventh day.

The subject invention concerns methods and materials for assessing a patient's likelihood of responsiveness to an immunosuppressive therapy. The subject invention is contemplated for use with patients having an autoimmune disorder. In an exemplified embodiment, the methods of the invention are used for assessing and / or treating a patient with MDS. In one embodiment, a method of the invention comprises analyzing T cells of a patient for dysregulation of CD4+ and / or CD8+ T cell subsets, and determining the patient's likelihood of responsiveness to IST based on the level of dysregulation of the patient's CD4+ and / or CD8+ T cell subsets. In one embodiment, an increased likelihood of patient responsiveness to IST is associated with an increased percentage of CD4+ and / or CD8+ effector memory T cells and / or terminal effector memory T cells, for a patient. The subject invention also concerns methods for treating a patient with an autoimmune disorder, such as MDS. In one embodiment, a method of the invention comprises determining if a patient is likely to respond to IST, wherein said determination is made using a method of the present invention for assessing likelihood of responsiveness to IST; and if the patient is determined to be one likely to respond to IST, administering an effective regimen of IST to the patient.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naive, 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.

The invention discloses chimeric antigen receptor-T cells secreting and expressing IL15RA-IL15 fusion proteins and CCL21 chemotactic factors as well as application thereof. Super IL15 can promote activation and proliferation of T (especially memory T) cells, NK cells and NKT cells; and CCL21 can recruit peripheral CCR7-positive initial T cells, memory T cells and dendritic cells (DC) into lymphoidtissue or tumor lesions so as to activate active anti-tumor immune response (such as cancer memory T cells) in the body, thereby significantly improving efficiency and remission rate, as well as reducing recurrence rate after remission.

The invention relates to a mannose modified co-loaded antigen and a double immuno-agonist phospholipid hybrid polymer vesicle as well as a preparation method and application thereof. A vaccine carriertakes an amphiphilic triblock copolymer as material, OVA is loaded in the hydrophilic inner cavity, IMQ is loaded in the hydrophobic membrane layer, DOTAP cationic layer is fitted with MPLA, and cationic lipid outer layer adsorbs outer layer OVA; phospholipid with reactive group is introduced to pass the targeted mannose ligand through covalently linked to the PEG-active distal end of the polymer-loaded vesicle surface, integrating the functions of active targeting of tumors, co-delivery of antigens and adjuvants and the like; the vesicle has the characteristics of small particle size, good dispersion, high antigen loading and good biocompatibility, etc., which can promote antigen uptake, DC activation and maturation, antigen cross-presentation, antigenic lymph node migration, lymphocyteactivation, effector T cell immune response, CD8<+> T and CD4<+> T cell responses, and memory T cells immune response.

The invention discloses an application of N-acetylcysteine in the in-vitro amplification of the absolute quantity of central memory T cells, and provides an optimal concentration for N-acetylcysteine to promote in-vitro amplification. The method is characterized in high safety, low cost, and the like. The method provides good technical support for general development of adoptive immunotherapy.

A Disclosed are methods for detecting and localizing a cell-specific antigen in a mammal, such as a human subject, comprising exposing peripheral blood mononuclear cells (PBMCs) of the mammal to an immunogenic peptide epitope of the antigen, under conditions for antigen-specific activation of T lymphocytes in the PBMCs, thereby producing antigen-specific T lymphocytes that at least bind to the cell-specific antigen. Labeled antigen-specific T lymphocytes are administered to the mammal, typically with-out IL-2, either intraperitoneally or intravenously. The distribution of these cells in the mammal is determined by imaging, thereby detecting and localizing cell-specific antigen in the mammal. Exposing PBMCs to the immunogenic peptide typically involves a cell-free peptide preparation and interleukin-2 (IL-2), but no additional cells such as antigen presenting cells (APC) separately pulsed with antigen. The antigen-specific T lymphocytes typically are cytolytic for cells expressing the cell-specific antigen and may comprise CD4+, CD8+, and / or CD45RO+ memory T cells.