Abstract: The present invention relates to a method for producing natural killer cells (hereinafter, referred to as “NK cells”), NK cells produced thereby, and a composition for treating cancers and infectious diseases containing the same. The present invention provides a method for producing NK cells, which maintain high cytotoxicity and cell viability to exhibit high therapeutic effects against cancers and infectious diseases and can be cultured ex vivo at high efficiency and high concentration. In addition, a culture method which maintains cell concentration at a constant level is used for the production of NK cells, and thus the overgrowth of the cells can be prevented so that the cells can be maintained at an optimal state. Particularly, even when the cells are thawed after freezing, the function of the cells is not impaired, and the NK cells can maintain high cell viability and cytotoxicity.

Abstract: The invention is directed to T cells and other cells that express chimeric NK-p30 receptors (“chimeric NKp30 T cells”), methods of making and using chimeric NKp30 T cells, and methods of using these chimeric NKp30 T cells, isolated populations thereof, and compositions comprising the same. In another aspect, said chimeric NKp30 T cells are further designed to express a functional non-TCR receptor. The disclosure also pertains to methods of making said chimeric NKp30 T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said chimeric NKp30 T cells, populations thereof, or compositions comprising the same.

Abstract: The present disclosure relates generally to the manufacture of regulatory T cells (Tregs) for use in immunotherapy. In particular, the present disclosure relates to robust approaches for the expansion of alloantigen-reactive Tregs ex vivo. Alloantigen-reactive Tregs produced in this way are suitable for the induction and/or maintenance of immunologic tolerance in recipients of allogeneic transplants.

Abstract: The invention is directed to a method of preparing B-cells that produce interleukin-10 (IL-10), or IL-10 per se, which comprises contacting one or more B-cells ex vivo with an isolated interleukin-35 (IL-35) protein, and culturing the one or more B-cells under conditions to provide one or more B-cells that produce IL-10. The invention also is directed to a method of suppressing the proliferation of lymphocytes in vitro or in vivo by contacting lymphocytes with an isolated IL-35 protein. The invention further is directed to a method of suppressing autoimmunity in a mammal by administering to the mammal an IL-35 protein or IL-10-producing B-cells.

Abstract: The present invention is directed to generating suppressor cells by treating naive T cells with a suppressor-inducing composition such as anti-CD3, anti-CD28, IL-2, TGF-?, or some combination thereof. Such suppressor cells are administered to patients to prevent or treat immune disorders and are allogeneic to the patient.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

Abstract: The present invention relates to the use of a peptide comprising or essentially consisting of a sequence motif as shown in SEQ ID NO: 1 for the preparation of a medicament for the treatment of Monoclonal Gammopathy of Undetermined Significance (MGUS) or of Smoldering Multiple Myeloma (SMM). Moreover, the present invention relates to the use of an activated T-cell specifically recognizing the peptide of the present invention or an antigen presenting cell which specifically presents a peptide epitope of the present invention for the preparation of a medicament for the treatment of Monoclonal Gammopathy of Undetermined Significance (MGUS) or of Smoldering Multiple Myeloma (SMM). The present invention also relates to a method for the ex vivo manufacture of an activated T-cell of the present invention comprising the steps of: a) obtaining T-cells from a sample of a subject suffering from MGUS or SMM, b) contacting said T-cells with a peptide of the present invention, and c) collecting the activated T-cells.

Abstract: The object of the present invention is to provide a cell that can exhibit physiological activity based on galectin-9, a method for producing the cell, and use of the cell. In order to achieve the above object, the cell of the present invention contains galectin-9, and the galectin-9 is expressed on a cell surface.

Abstract: Compositions comprising human Tr1 cells directed to a food antigen from common human diet and methods for treating an intestinal inflammatory condition.

Abstract: The present invention provides cell compositions and methods of using treating disorders, such as inflammatory disorders, such as atherosclerosis and cardiovascular disease.

Abstract: A method of treating a cellular proliferative disorder in a subject by obtaining from a subject a bodily fluid sample containing a plurality of cells, incubating the sample with EDTA or heparin in a container until the sample is separated into an upper layer and a lower layer, collecting the upper layer, isolating from the upper layer a population of somatic stem cells that are 0.3-6.0 micrometers in size, differentiating the somatic stem cells to dendritic cells in a medium containing GCSF, SCF, EGF, PDGF, bFGF, and IL-3, purifying the dendritic cells, contacting the dendritic cells thus purified with a cancer antigen, and administrating an effective amount of the dendritic cells presenting the cancer antigen to a subject in need thereof.

Abstract: Isolated pluralities of T cells which recognize at least one epitope of a mucosally restricted antigen and pharmaceutical compositions comprising the same are disclosed. Methods of making a plurality of T cells that recognize at least one epitope of a mucosally restricted antigen are also disclosed. Methods of treating an individual who has been diagnosed with cancer of a mucosal tissue or preventing such cancer in an individual at elevated risk are disclosed as are nucleic acid molecules that comprise a nucleotide sequence that encode proteins that recognize at least one epitope of a mucosally restricted antigen and T cells comprising such nucleic acid molecules.

Abstract: The invention relates to therapy and methods of applying the therapy to a patient. The invention includes the introduction of immature dendritic cells into the patient and the introduction of anti-TNF antibody into the patient. The immature dendritic cells are introduced intratumorally and/or through vessel and the anti-TNF antibody is introduced intratumorally and/or through vessel and/or subcutaneously. The immature dendritic cells can be formed by collecting monocyte cells from the patient and culturing the cells in a culture medium. The invention can be effective to regress, reduce or eliminate tumor cells in tumor tissue of the patients, including metastasized tumors. Further, the treatment of the invention is effective in the absence of conventional therapy, such as radiotherapy and chemotherapy.

Abstract: Methods of making activated immunostimulatory cell compositions, activated immunostimulatory cell compositions, and methods of using those compositions to stimulate therapeutic immune response to infectious organisms are described.

Abstract: Methods and compositions related to the use of a protein with kynureninase activity are described. For example, in certain aspects there may be disclosed a modified kynureninase capable of degrading kynurenine. Furthermore, certain aspects of the invention provide compositions and methods for the treatment of cancer with kynurenine depletion using the disclosed proteins or nucleic acids.

Abstract: Described herein is a novel, highly efficient system to remove erythrocytes and purify leukocytes would raise the quality of UCB and other transplant grafts, thereby significantly improving patient outcomes.

Abstract: The present invention includes compositions and methods for the diagnosis and treatment of lung cancer with a recombinant tumor-associated antigen loaded antigen presenting cell that generates a cytotoxic T lymphocyte specific immune response to at least one of SP17, AKAP-4, or PTTG1 expressed by one or more lung cancer cells.

Abstract: The invention relates to therapy and methods of applying the therapy to cancer patients. The invention includes introducing intratumorally cytotoxic T lymphocyte and/or NKT cells, and prior to, coincident with, or following introducing intratumorally the cytotoxic T lymphocyte and/or NKT cells, introducing intratumorally anti-TNF and/or anti-IL-10 to the patient. The cytotoxic T lymphocyte and/or NKT cells can be induced by the intratumoral introduction of immature dendritic cells to the patient. This therapy of the invention can be effective to regress, reduce or eliminate tumor cells in tumor tissue of the patients in the absence of radiation therapy.

Abstract: Disclosed herein are methods and compositions for modulating the expression of a HLA locus, including cells that lack expression of one or more classic HLA genes but are not targeted by Natural Killer (NK) cells for lysis.

Abstract: The invention discloses novel methods, compositions of matter, and kits for the treatment of disorders affecting the hematopoietic system. Patients are administered an autologous cellular mixture derived from adipose stromal vascular fraction, said cellular mixture comprising endothelial cells, endothelial progenitor cells, T regulatory cells, monocytes, and hematopoietic stem cells. In one embodiment, treatment is provided for patients suffering from inflammatory disorders including aplastic anemia.

Abstract: The present invention relates to methods and compositions for use in inducing tumor-specific antibody mediated complement-dependent cytotoxic response in an animal having a tumor comprising administering to said animal a composition comprising a replication competent oncolytic virus wherein administration of the composition induces in the animal production of antibodies that mediate a CDC response specific to said tumor.

Abstract: Methods of making activated immunostimulatory cell compositions, activated immunostimulatory cell compositions, and methods of using those compositions to stimulate therapeutic immune responses to tumors are described.

Abstract: Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

Abstract: An apparatus that allows for separating and collecting a fraction of a sample. The apparatus, when used with a centrifuge, allows for the creation of at least three fractions in the apparatus. It also provides for a new method of extracting the buffy coat phase from a whole blood sample. A buoy system that may include a first buoy portion and a second buoy member operably interconnected may be used to form at least three fractions from a sample during a substantially single centrifugation process. Therefore, the separation of various fractions may be substantially quick and efficient.

Abstract: Embodiments of the invention employ methods and compositions for enhancing potency of immune cells that express one or more therapeutic proteins. In certain cases, the methods modulate expression of a CAR transgene in an immune cell, such as a T cell. Specific embodiments employ the exposure of cells and/or individuals to be treated with the cells with an effective amount of at least one agent that upregulates expression of the therapeutic protein, such as a mitogen, histone deacetylase inhibitor, and or DNA methyltransferase inhibitor.

Abstract: The present disclosure relates to methods of inducing tolerance to lung allograft transplantation. These methods comprise increasing nitric oxide, increasing suppressor CD8+ T cells and/or suppressing deleterious CD8+ and CD4+ T cells.

Abstract: The invention relates to a method for identifying T-cell stimulating protein fragments using the following steps: a) detecting the amino acid sequence of an antigen; b) subdividing the found amino acid sequence of the antigen into protein fragments; c) synthesizing at least one protein fragment; d) incubating a suspension containing t-cells with the protein fragments; e) identifying an induced T-cell cytokine or activation marker by flow-through cytometry, and; f) assigning the T-cells, with which T-cell cytokines and/or activation markers were identified, to the protein fragments which were incubated with the T-cells. The corresponding protein fragments/peptides are synthetically produced with the assistance of the detected positive sequence, and said corresponding protein fragments/peptides can be utilized to produce a medicament for immunostimulation.

Abstract: An apparatus for the preparation of cells for implantation into a living body is disclosed. The apparatus comprises a vessel substantially impermeable to gaseous oxygen; and fluid within said vessel, the fluid having a maximal dissolved oxygen capacity substantially equivalent to normal saline yet having a hypoxic oxygen concentration between about 0% to about 5% of said maximal dissolved oxygen capacity. The bag oxygen concentration level remains low when the apparatus is stored at 22°-25° C. in normal atmospheric conditions for a period of at least 30 days. The present invention simplifies the process of achieving donor cell hypoxic preconditioning for cell implantation, and may be used to bathe said cells to be transplanted for a sufficient time to activate the hypoxic metabolic pathway.

Abstract: The present invention concerns methods of generating CTLs that are able to target at least one antigen from two or more viruses. The method includes exposing mixtures of peptides for different antigens to the same plurality of PBMCs and, at least in certain aspects, expanding the cells in the presence of IL4 and IL7.

Abstract: Provided herein are methods of producing natural killer cells using a two-step expansion and differentiation method. Also provided herein are methods of suppressing tumor cell proliferation, of treating individuals having cancer or a viral infection, comprising administering the NK cells produced by the method to an individual having the cancer or viral infection.

Abstract: The present specification discloses regulatory T cells, compositions including regulatory T cells, methods of identifying, isolating, enriching, obtaining, and/or expanding regulatory T cells or subset populations thereof, kits including components useful for performing such methods, and methods of treating an immune-based disorder in an individual by administering regulatory T cells or compositions comprising such regulatory T cells to an individual in need thereof.

Abstract: Provided herein are sphingolipid compounds that are useful for activating natural killer T cells. Also provided are methods for treating or preventing a disease or disorder that is treatable by activating the immune system by stimulating natural killer T cells. The compounds are therefore useful for treating or reducing the likelihood of occurrence of an immune diseases and disorders, such as autoimmune diseases or disorders. The compounds may also be used for treating or reducing the likelihood of occurrence of a microbial infection or for treating or reducing the likelihood of occurrence of a cancer in a subject by administering the sphingolipid compounds described herein.

Abstract: Disclosed herein are methods and compositions for expanding T-regulatory cells (“Treg” cells), resulting in “conditioned Treg cells.” Also disclosed herein are methods and compositions useful for modulating an autoimmune reaction and for treating or ameliorating immune-related diseases, disorders and conditions using the conditioned Treg cells.

Abstract: The present invention provides a method of treating a disease in a subject in need thereof via non-syngeneic graft administration without or with reduced concomitant graft rejection. The method comprises administering to the subject a therapeutically effective graft being non-syngeneic with the subject, and a dose of tolerogenic cells being non-syngeneic with both the subject and the graft for preventing or reducing graft rejection in the subject, thereby treating the disease in the subject.

Abstract: The present disclosure provides biomaterials and methods for preventing and minimizing progression of cartilage and/or connective tissue damage. Also provided herein are biomaterials and methods for alleviating and/or reducing the risk for developing arthritis (e.g., osteoarthritis) associated with joint injury and/or joint surgery.

Abstract: Materials and methods for obtaining populations of lymphocytes and administering the population of lymphocytes to a subject are disclosed herein. In particular, disclosed herein are materials and methods for obtaining lymphocyte populations that contain at least about 0.5×109 NK cells per kilogram weight of the subject from which the cells are harvested.

Abstract: The present invention is directed to compositions and methods for treatment of ischemic diseases and conditions, particularly myocardial, CNS/brain and limb ischemia. More particularly, the present invention provides methods of treating disorders by administering monocytes obtained from blood, including umbilical cord blood, peripheral blood, or bone marrow to an individual in need of treatment, wherein the drug is administered to the individual at a time point specifically determined to provide therapeutic efficacy. In one embodiment, the cells are for injection into ischemic myocardium for the treatment of angina.

Abstract: A method is provided for preventing rejection by an immune system of a recipient subject of a tissue transplanted from a donor subject into the recipient subject without the need for long-term administration of non-specific immunosuppressive drugs.

Abstract: The invention provides peptides comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) mucin 1 (MUC1) and analogs thereof, which can be used in vaccine prevention or therapy of cancer, as well as a nucleic acid encoding the peptide, a vector comprising the nucleic acid, a cell comprising the peptide, nucleic acid, or vector, and compositions thereof.

Abstract: A subpopulation of peripheral blood mononuclear cells (PBMCs) that is substantially devoid of CD3+ cells, CD19+ cells, CD56+ cells and optionally of CD16+ cells, for use in treatment of CNS injury is provided.

Abstract: Granulin-epithelin precursor (GEP), a pluripotent growth factor, is a hepatic oncofetal protein defining a cancer stem cell (CSC) population in liver cancer. The present invention provides the use of GEP inhibitors (including anti-GEP antibody) for inhibiting immune evasion by liver cancer cells and for eliminating liver cancer stem cells.

Abstract: The invention is directed to methods of measuring an immune response by comparing sequence-based clonotype frequency data from successively measured clonotype profiles. In particular, the invention includes immunotherapies of cancers, such as lymphomas, that include sensitive pre- and post-vaccination sequence-based measurements of changes in a patient's immune repertoire, thereby providing a sensitive measure of the likelihood of treatment success.

Abstract: The present invention comprises a method of treatment of an autoimmune disease involving a specific tolerance induction (“STI”) event, wherein the method includes: collecting a first sample from the patient prior to the STI event; detecting an STI event or performing a procedure that correlates in time to an STI event; collecting a second sample from the patient after the STI event; preparing lymphocytes from the first and second samples; preparing and sequencing DNA or cDNA from the prepared lymphocytes; identifying sequences of prevalent T or B cell receptors (“prevalent receptor sequences”) among the lymphocytes of the second sample; selecting a regulatory lymphocyte that carries at least one prevalent receptor sequence, which selected regulatory lymphocyte (i) expresses at least one prevalent receptor sequence or (ii) is generated from an autologous or allogeneic naïve lymphocyte, which naïve lymphocyte is engineered and induced to become a regulatory lymphocyte that expresses at least one prevalent recep

Abstract: Compositions and methods are provided for generating T cells having a regulatory phenotype from conventional T (Tconv) cells. Such compositions and methods include culturing isolated, naïve Tconv cells with an effective amount of interleukin-35 (IL-35) until the cells have the regulatory phenotype. Also provided are methods to treat subject having or susceptible to having various disorders including, for example, immune system disorders with the T cells having the regulatory phenotype.

Abstract: Provided are TCL1 peptides that bind to MHC I (HLA-A2) on tumor cells or other antigen-presenting cells and are recognized by T-cell receptors on T cells. The TCL1 peptides may be therapeutically used to treat a cancer, such as a B cell malignancy, leukemia, or lymphoma. Methods for expanding a population of T cells that target TCL1 are also provided.

Abstract: Disclosed are methods and compositions for treating cancer that involved an isolated double stranded ribonucleic acid (dsRNA) molecule that inhibits the expression of Hsp-27.

Abstract: The present invention relates to immunomodulatory cells, methods for providing immunomodulatory cells, and therapeutic uses of the cells for the immune modulation of mammals in need thereof.

Abstract: High-affinity variants of the DMF5 TCR, and methods of use thereof for the treatment and imaging of cancer in a patient.

Abstract: Tolerogenic populations of dendritic cells are provided, where the dendritic cells are characterized by expression of select tissue-specific homing receptors including the chemokine receptors CCR9; or CMKLR1; or the integrin CD103. The dendritic cells may be conventional/myeloid or plasmacytoid dendritic cells. The cells may be isolated from lymphoid tissue, from blood, or from in vitro culture, e.g. bone marrow culture, etc. Methods are provided for their identification, isolation and targeting in immunotherapeutic interventions in suppressing inflammatory disorders including autoimmunity, transplantation responses and allergic diseases. In some embodiments dendritic cell populations are fixed to render them immunosuppressive, thus allowing the cells to be typed and banked for future use.

Abstract: A method of inducing or promoting hair growth on the scalp of a subject, comprising the steps of (i) providing an ECM composition including at least one ECM material, (ii) administering inciting event means to a target skin location on the subject to induce an inciting event, and (iii) administering a therapeutically effective amount of said ECM composition to the target skin location. In some embodiments, the ECM composition includes at least one additional biologically active agent.