Abstract: The present disclosure relates to compositions and methods for using cells having chemically-induced fusion protein complexes to spatially and temporally control immune cell signal initiation and downstream responses for treating disease.

Abstract: Provided are methods for improving cell-based therapies by co-administration with an agent that increases the production and or levels of epoxygenated fatty acids, as well as kits, stents and patches for co-administering stem cells with an agent that increases the production and/or levels of epoxygenated fatty acids.

Abstract: The present disclosure relates to a novel process for expanding T cells, such as autologous T cells, cell populations therefrom, pharmaceutical compositions comprising the said cell populations and use of the cells and compositions for treatment, particular the treatment or prophylaxis of virus infection and/or cancer, for example in immune compromised or immune competent human patients.

Abstract: Human progenitor T cells that are able to successfully engraft a murine thymus and differentiate into mature human T and NK cells are described. The human progenitor T cells have the phenotype CD34+CD7+CD 1a?CD5? or CD34+CD7+CD1a?CD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells by coculture with cells expressing a Notch receptor ligand (OP9-DL1 or OP9-DL4). Such cells are useful in a variety of applications including immune reconstitution, the treatment of immunodeficiencies and as carriers for genes used in gene therapy.

Abstract: Modified natural killer cells, pharmaceutical compositions comprising the modified natural killer cells and at least one pharmaceutically acceptable carrier or excipient, uses of the modified natural killer cells, and methods for identifying depleted natural killer cells and culturing the modified natural killer cells are provided.

Abstract: The present invention provides a cell which co-expresses a first chimeric antigen receptor (CAR) and second CAR at the cell surface, each CAR comprising: (i) an antigen-binding domain; (ii) a spacer (iii) a trans-membrane domain; and (iv) an endodomain wherein the antigen binding domains of the first and second CARs bind to different antigens, and wherein one of the first or second CARs is an activating CAR comprising an activating endodomain and the other CAR is an inhibitory CAR comprising a ligation-off inhibitory endodomain.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: The present invention relates to a peptide derivative for regulating the thymic stromal lymphoid protein-mediated signaling and a pharmaceutical composition including the peptide derivative for preventing and treating allergy and asthma diseases and, more particularly, to a peptide derivative represented by Chemical Formula 1 and a pharmaceutical composition including the peptide derivative for preventing and treating allergy and asthma diseases. According to the present invention, provided are a peptide derivative capable of effectively inhibiting the formation of an inflammatory response of allergy and asthma diseases and a pharmaceutical composition including the peptide derivative. By using the present invention, various allergy and asthma diseases can be fundamentally prevented or treated.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

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: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Protected fluorescent reagent compounds and their methods of synthesis are provided. The compounds are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The compounds contain fluorescent dye elements, that allow the compounds to be detected with high sensitivity at desirable wavelengths, binding elements, that allow the compounds to be recognized specifically by target biomolecules, and protective shield elements, that decrease undesirable contacts between the fluorescent dye elements and the bound target biomolecules and that therefore decrease photodamage of the bound target biomolecules by the fluorescent dye elements.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: Methods of obtaining a cell population enriched for tumor-reactive T cells, the method comprising: (a) obtaining a bulk population of peripheral blood mononuclear cells (PBMCs) from a sample of peripheral blood; (b) specifically selecting CD8+T cells that also express PD-1 and/or TIM-3 from the bulk population; and (c) separating the cells selected in (b) from unselected cells to obtain a cell population enriched for tumor-reactive T cells are disclosed. Related methods of administering a cell population enriched for tumor-reactive T cells to a mammal, methods of obtaining a pharmaceutical composition comprising a cell population enriched for tumor-reactive T cells, and isolated or purified cell populations are also disclosed.

Abstract: A method of carrying out adoptive immunotherapy by administering a subject an antigen-specific cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount is described. In the method, the CTL preparation is preferably administered as a preparation of an in vitro antigen-stimulated and expanded primate CTL population, the CTL population: (i) depleted of FoxP3+ T lymphocytes prior to antigen stimulation; (ii) antigen-stimulated in vitro in the presence of interleukin-21; or (iii) both depleted of FoxP3+ T lymphocytes prior to antigen stimulation and then antigen-stimulated in vitro in the presence of interleukin-21. Methods of preparing such compositions, and compositions useful for carrying out the adoptive immunotherapy, are also described.

Abstract: The influence of TF, endothelial cell protein C receptor (EPCR) and protease activated receptor-1 (PAR1) on tumor growth of malignant pleural mesothelioma (MPM) is disclosed. MPM cells that lack or express TF, EPCR or PAR1 and a murine orthotopic model of MPM led to the discovery that intrapleural administration into nude mice of REN MPM cells expressing TF and PAR1 but lacking EPCR and PAR2 generated large pleural cavity tumors. Suppression of TF or PAR1 expression markedly reduced tumor growth. Overexpression of TF in non-aggressive MPM cells expressing EPCR and PAR1 but exhibiting minimal levels of TF failed to alter their tumorigenicity. Introduction of EPCR expression in aggressive MPM cells attenuated tumor growth whereas EPCR silencing in non-aggressive MPM cells overexpressing TF increased tumorigenicity of non-aggressive cells. Expression of EPCR by MPM cells suppresses tumor growth and treats MPM.

Abstract: Provided herein are placental perfusate, placental perfusate cells, placenta-derived intermediate natural killer cells, combined natural killer cells from placenta and umbilical cord blood, and combinations thereof. Also provided herein are compositions comprising the same, and methods of using placental perfusate, placental perfusate cells, placenta-derived intermediate natural killer cells, and combined natural killer cells and combinations thereof, to suppress the growth or proliferation of tumor cells, cancer cells, and the like, and to treat individuals having tumor cells. Also provided herein are methods of treating an individual having a tumor or graft-versus-host disease with placental perfusate, placental perfusate-derived cells, natural killer cells from placenta, e.g., from placental perfusate, and/or combined natural killer cells comprising natural killer cells from placenta, e.g., from placental perfusate, and umbilical cord blood.

Abstract: The present invention relates to, among others, an in vitro method of modifying a cell graft containing immune cells comprising the steps of incubating a cell graft containing immune cells with an anti CD4 antibody wherein said incubating is carried out for from 1 minute to 7 days, b) removing unbound antibody from said graft; as well as to corresponding modified grafts and uses. The invention further relates to the modification of antibodies reactive to the CD4 human leukocyte antigen to provide anti-CD4 antibodies that have a reduced number of potential T-cell epitopes but retain the ability to bind to CD4, such as to an anti human CD4-antibody comprising a heavy chain immunoglobulin variable domain (VH) and a light chain immunoglobulin variable domain (VL), wherein at least one T cell epitope located outside the CDRs of said immunoglobulin variable domains is removed from said immunoglobulin variable domains.

Abstract: The present invention discloses a use of dendritic killer cell population for manufacturing medication. The dendritic killer cell population is generated by culturing peripheral blood mononuclear cells with effective amounts of various cytokines for an appropriate time period, and the conserved cytokine is IL-15. Meanwhile a pharmaceutical composition comprises the above dendritic killer cell population for treating cancers is also disclosed in the present invention.

Abstract: Methods and compositions are provided for combined transplantation of a solid organ and hematopoietic cells to an HLA mismatched recipient, where tolerance to the graft is established through development of a persistent mixed chimerism. An individual with persistent mixed chimerism, usually for a period of at least six months, is able to withdraw from the use of immunosuppressive drugs after a period of time sufficient to establish tolerance.

Abstract: The present invention relates to B7-H4-specific chimeric antigen receptor compositions and methods of use thereof.

Abstract: A technique is needed which can amplify NK cells in vitro and prepare optimum number of NK cells for the adoptive immunotherapy. A method for amplifying NK cells is provided which comprises steps of: preparing cell population which is comprised of NK cells, removing T cells from the cell population which is comprised of NK cells, and, after removal of T cells, cultivating the remaining cells in a medium supplemented with 2500 to 2831 IU/mL of IL-2. The method for amplifying NK cells of the present invention may comprise a step of removing hematopoietic progenitor cells from the cell population. The present invention provides a pharmaceutical composition for adoptive immunotherapy, comprising NK cells which are prepared by the amplifying method of the present invention.

Abstract: The present invention relates to CD4+ T cells, more specifically cytolytic or cytotoxic CD4+ T-cells and methods of obtaining and identifying them.

Abstract: The present invention is directed to in vitro methods for promoting expression of G-protein coupled receptor 15 (GPR15) on T cells, GPR15+ enriched populations of T cells generated using these methods and compositions thereof, as well as methods of using these T cell populations for therapeutic purposes.

Abstract: The present invention relates to a method for producing a cell line expressing a stabilized functional single chain-antigen-recognizing genetic construct (scARC), comprising a genetic construct of the human scARC to be expressed, comprising the domains huV1/2—Li-huV2/1—C4/3 and a genetic construct comprising the corresponding hetero-/(homo-)dimeric domain C3/4, containing xenogenic, in its special case murine amino acid exchanges in the domains C4/3 and C3/4, wherein co-expression of the genetic constructs of the scARC-fragments occurs through the cell. Preferably, the scARCs are single chain-TCRs (scTCRs) or antibody-scFv-fragments, which further preferably recognize tumor associated peptide antigens (TAA). The present invention further relates to a gp100-protein-specific T-cell response mediated ?/? T-cell receptor rationally mutated by means of the method of the present invention and its uses.

Abstract: [Problem] To provide an anti-human TSLP receptor antibody that specifically binds to human TSLP receptor and inhibits an action of human TSLP through human TSLP receptor. [Means for Solution] An anti-human TSLP receptor antibody had been studied by the present inventors, and an anti-human TSLP receptor antibody comprising a heavy chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 118 of SEQ ID NO: 1 and a light chain variable region consisting of the amino acid sequence of amino acid numbers 1 to 108 of SEQ ID NO: 3 was provided. It was revealed that the anti-human TSLP receptor antibody inhibits expression of TARC mRNA induced by TSLP and production of MDC proteins, and suppressed an allergic reaction in a monkey Ascaris antigen sensitization model, and then the present invention was completed.

Abstract: Embodiments of the present invention provides bone graft compositions, and methods for their use and manufacture. A bone graft composition may include a first amount of non-demineralized cancellous bone. The composition may further include a second amount of demineralized cancellous bone. The composition may also include a third amount of demineralized cortical bone. The non-demineralized cancellous bone, the demineralized cancellous bone, and the demineralized cortical bone may be obtained from the same cadaveric donor.

Abstract: A method of generating a CD4+FoxP3+ Treg cell, the method includes administering at least one complement antagonist to a naive CD4+ T cell at an amount effective to substantially inhibits C3a receptor (C3aR) and/or C5a receptor (C5aR) signal transduction in the CD4+ T cell, induce TGF-?1 expression of the CD4+ T cell, and induce differentiation of the of the naive CD4+ T cell into a CD4+FoxP3+ Treg cell.

Abstract: The present invention provides a therapeutic composition comprising: (i) Trolox, Na+, K+, Ca2+, Mg2+, Cl?, H2PO4?, HEPES, lactobionate, sucrose, mannitol, glucose, dextran-40, adenosine, glutathione; and (ii) stem cells or progenitor cells, wherein the composition does not comprise a dipolar aprotic solvent, in particular DMSO. The present invention also relates to methods of formulating said composition for cryopreservation and subsequent direct administration to a patient, and medicaments comprising said composition.

Abstract: The present invention provides compositions and methods for generation of an anti-influenza immune response. In particular, conserved T cell epitopes within matrix protein and nucleoprotein components of influenza virus have been identified and further screened for those structures that will bind either or both of HLA I and II molecules. Methods for vaccinating subjects with formulations of such peptides for the treatment or prevention of influenza infaction also are described.

Abstract: A method for producing NK cells from pluripotent stem cells, which includes culturing pluripotent stem cells in a first serum-free medium, aggregating the undifferentiated stem cells to form embryoid bodies, which are cultured to produce hematopoietic precursor cells, and culturing the precursor cells in a serum-free medium to produce the NK cells. Methods for using such NK cells, e.g., in the treatment of cancer and infectious disease are also provided.

Abstract: The invention relates to a method of inducing Foxp3 expression in a T cell comprising (i) stimulating a T cell (ii) inhibiting signalling via PI3K alpha or PI3K delta or m-TOR or Akt in said T cell, wherein said inhibition is commenced 10 to 22 hours after the stimulation of (i). The invention also relates to certain uses of PI3K inhibitors, PI3K inhibitors for particular uses, and kits.

Abstract: Disclosed herein are chimeric receptors comprising an extracellular domain with affinity and specific for the Fc portion of an immunoglobulin molecule (Ig) (e.g., an extracellular ligand-binding domain of F158 FCGR3A or V158 FCGR3A variant); a transmembrane domain (e.g., a transmembrane domain of CD8?); at least one co-stimulatory signaling domain (e.g., a co-stimulatory signaling domain of 4-1BB); and a cytoplasmic signaling domain comprising an immunoreceptor tyrosine-based activation motif (ITAM) (e.g., a cytoplasmic signaling domain of CD3?). Also provided herein are nucleic acids encoding such chimeric receptors and immune cells expressing the chimeric receptors. Such immune cells can be used to enhance antibody-dependent cell-mediated cytotoxicity and/or to enhance antibody-based immunotherapy, such as cancer immunotherapy.

Abstract: An object of the present invention is to establish a method that enables safe and convenient large-scale preparation of regulatory dendritic cells. The present invention provides a method for preparing regulatory dendritic cells, which comprises culturing cells that can be induced to result in regulatory dendritic cells in the presence of a [1,2,4]triazolo[1,5-a]pyrimidine derivative.

Abstract: Provided is a method for monitoring a gene mutation associated with a cancer in a patient over time. Also provided is a method of selecting and/or applying treatment or therapy for a subject.

Abstract: The present invention provides dendrimer conjugates. The present invention provides a composition comprising a dendrimer conjugate and a cell, such as a cell covered with dendrimer conjugates, in which dendrimer conjugates home the cell to a target tissue.

Abstract: Cancer antigens containing mutations in an expressed gene of cancer cells from a cancer patient are identified. Sequences from cancer cells obtained using a parallel sequencing platform are selected by comparing to the patient's normal genes or to normal genes from an HLA-matched individual. Sequences are further selected by identifying an HLA supertype of the cancer patient and selecting for that HLA supertype, sequences that have a particular amino acid at the mutant position and/or corresponding wild-type position in the effected gene. Peptides containing cancer antigens (i.e., mutations—once a mutation is defined, what makes it an immunogen is its ability to induce an immune response) are optionally tested for binding to HLA antigens of the cancer patient. Peptides containing the cancer antigens are evaluated for activating T cells (e.g., helper T lymphocytes and cytotoxic T lymphocytes (CTL)) cell lines from the cancer patient or from an HLA-matched donor.

Abstract: This invention pertains to cancer immunotherapy, by providing a proinflammatory dendritic cell (DC), which has been stimulated to maturation ex vivo by specific treatment, a method for such treatment and a composition comprising the proinflammatory DC. The DC may be used as a cell based immunotherapy for inhibiting tumor cell proliferation.

Abstract: The invention is based upon the discovery that T regulatory type 1 (Tr1) cells express particular cell surface markers that allow for their selection, enrichment, isolation, purification and administration. The ability to use the particular markers described herein to select, enrich, isolate, purity and administer Tr1 cells allows for improved methods of Tr1 therapies for treating a wide variety of diseases and disorders.

Abstract: The invention provides methods and compositions for administration of allogeneic lymphocytes as an an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells. Depletion of CD8+ T cells from the donor lymphocyte infusion reduces the risk of sustained engraftment and graft-versus-host disease. Removal of regulatory T cells from the infused population may augment the ability of non-regulatory T cells to provide help for endogenous effectors of anti-tumor immunity. Allogeneic T cell therapy is typically given in the context of allogeneic stem cell transplantation, in which the patient receives highly immunosuppressive conditioning followed by an infusion of a stem cell graft containing unselected populations of mature T cells. In the treatment described here, the graft is engineered to minimize the possibility of sustained donor cell engraftment, and the anti-tumor effector T cells derive from the host.

Abstract: The present invention relates to a melanoma antigen peptide comprising the amino acids sequence selected in the group consisting of SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, SEQ ID NO: 14 or SEQ ID NO: 15 or a function-conservative variant thereof. Moreover the invention also relates to a melanoma antigen peptide according to the invention for use in the prevention or the treatment of melanoma in patient.

Abstract: The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Abstract: The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to 30 peptide sequences and their variants derived from HLA class I and class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Abstract: Described herein are methods for treating and preventing graft versus host disease using ACK inhibitors. The methods include administering to an individual in need thereof an ACK inhibitor such as ibrutinib for treating and preventing graft versus host disease.

Abstract: Methods are provided for treating, mitigating or protecting from radiation-induced injury using bone marrow stromal cells expanded in culture, adipose-tissue derived non-adherent stromal cells, or the culture supernatant thereof.

Abstract: The present disclosure provides methods for generating enhanced affinity T cell receptors by agonist selection of hematopoietic progenitor cells expressing an antigen specific TCR? cultured with stromal cells expressing Delta-like-1 or Delta-like-4, compositions prepared from such methods, and uses of thereof.