Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Abstract: 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.

Abstract: Nucleases and methods of using these nucleases for modification of an HPRT locus and for increasing the frequency of gene modification at a targeted locus and clones and for generating animals.

Abstract: Methods and compositions relating to the production of induced pluripotent stem cells (iPS cells) are disclosed. For example, induced pluripotent stem cells may be generated from CD34+ hematopoietic cells, such as human CD34+ blood progenitor cells, or T cells. Various iPS cell lines are also provided. In certain embodiments, the invention provides novel induced pluripotent stem cells with a genome comprising genetic rearrangement of T cell receptors.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: Isolated pluralities of T cells which recognize at least one epitope of an intestinal cancer antigen or CNS cancer antigen and pharmaceutical compositions comprising the same are disclosed. Methods of making a plurality of T cells that recognize at least one epitope of an intestinal cancer antigen or CNS cancer 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 an intestinal cancer antigen or CNS cancer antigen and T cells comprising such nucleic acid molecules.

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 fluorescent proteins, in particular green fluorescent proteins (GFPs), with increased activity in cells, and thus increased signal strength. A further aspect of the present invention relates to the use of peptides for increasing the expression and/or stability of a protein in a cell.

Abstract: The present invention relates to new methods to promote sialylation of glycoconjugates, including recombinant glycoproteins, in glycoconjugate production systems. The invention relates to methods to promote efficient glycoconjugate sialylation in recombinant expression systems, by providing simpler and more economical ways to produce large intracellular pools of sialic acid precursors. The invention is directed to nucleic acids, vectors, and cells harboring vectors comprising nucleic acids encoding enzymes involved in the synthesis of sialic acid precursors, and cells harboring these nucleic acids in combination with nucleic acids encoding glycosyltransferases, including sialyltransferases, to facilitate the production of humanized recombinant glycoproteins in bacterial, fungal, plant, and animal cell expression systems.

Abstract: Provided herein is a method for assessing the risk of potential adverse effects for a human patient mediated by the administration of a CD19.times.CD3 bispecific antibody to said patient comprising determining the ratio of B cells to T cells of said patient, wherein a ratio of about 1:5 or lower is indicative for a risk of potential adverse effects for said patient.

Abstract: The disclosure provides a chimeric antigen receptor (CAR) comprising a) an antigen binding domain of HA22, a transmembrane domain, and an intracellular T cell signaling domain; or b) an antigen binding domain of BL22, a transmembrane domain, and an intracellular T cell signaling domain comprising CD28 and/or CD137. Nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding portions thereof, and pharmaceutical compositions relating to the CARs are disclosed. Methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal are also disclosed.

Abstract: Disclosed herein are methods of modulation of the viability of a cell. Further disclosed herein are methods of modulating an immune response. Further disclosed herein are methods of identifying agents capable of modulation of the viability of a cell or an immune response. Further disclosed herein are agents and compositions capable of modulation of the viability of a cell or an immune response.

Abstract: Integration of costimulatory signaling domains within a tumor targeting chimeric antigen receptor (CAR), such as the IL13R?2 specific IL13-zetakine (IL13?), enhances T cell-mediated responses against tumors even in the absence of expressed ligands for costimulatory receptors.

Abstract: The document provides nucleic acids, polypeptides, and viruses containing nucleic acids and/or polypeptides. The document also provides methods for using viruses to treat cancer patients. Specifically, the document provides nucleic acid molecules encoding viral hemagglutinin (H) polypeptides, viral H polypeptides, and viruses containing nucleic acids and/or H polypeptides. Such viruses are useful for vaccinations and for treating cancer patients as the viruses are not shed.

Abstract: The invention provides human cells, particularly human T cells, comprising a murine T Cell Receptor (TCR) having antigen specificity for the cancer antigen gp100. Isolated or purified TCRs having antigenic specificity for amino acids 154-162 of gp100 (SEQ ID NO: 1), as well as related polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, or antigen binding fragments thereof, conjugates, and pharmaceutical compositions, are further provided. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host comprising the use of the inventive materials described herein.

Abstract: The present invention relates generally to a fusion protein that when displayed on a cell can convert a negative signal into a positive signal in the cell. The fusion protein is a chimeric protein in that the protein comprises at least two domains, wherein the first domain is a polypeptide that is associated with a negative signal and the second domain is a polypeptide that is associated with a positive signal. Thus, the invention encompasses switch receptors that are able to switch negative signals to positive signals for enhancement of an immune response.

Abstract: The invention relates to the use of nanopatterned surfaces. It also relates to a method for enriching or isolating cellular subpopulations. To create a simple, versatile and specific method for enriching or isolating cellular subpopulations from a complex mixture, the invention proposes the use of nanopatterned surfaces for isolating and enriching cellular subpopulations from a complex mixture.

Abstract: The invention provides T cell receptors (TCRs) having antigenic specificity for a cancer antigen, e.g., tyrosinase. Also provided are related polypeptides, proteins, nucleic acids, recombinant expression vectors, isolated host cells, populations of cells, and pharmaceutical compositions. The invention further provides a method of detecting the presence of cancer in a host and a method of treating or preventing cancer in a host using the inventive TCRs or related materials.

Abstract: This invention relates to the culture of dendritic cells from human embryonic stem (ES) cells. Human ES cells are first cultured into hematopoietic cells by co-culture with stromal cells. The cells now differentiated into the hematopoietic lineage are then cultured with GM-CSF to create a culture of myeloid precursor cells. Culture of the myeloid precursor cells with the cytokines GM-CSF and IL-4 causes functional dendritic cells to be generated. The dendritic cells have a unique phenotype, as indicated by their combination of cell surface markers.

Abstract: The composition of activated CD4 cells is derived from a healthy human donor. The composition from the healthy human donor is suspended in an infusion media and packaged in a vehicle for administration to a subject to treat disease.

Abstract: Obesity is associated with a state of chronic low-grade inflammation and the present invention establishes that adipose-resident natural killer T (NKT) cells attenuate inflammation in adipose tissue and improves systemic glucose homeostasis in mice at different stages of obesity. Accordingly, the present invention provides methods of treating type-2 diabetes or those at risk for type-2 diabetes using activators of adipose-resident NKT cells. Such activators include particular glycolipids (e.g., a-galactosyl-ceramide and its analogs other than sulfated analogs) and cytokines that promote M2 macrophage polarization. The invention also includes methods to screen for activators of adipose-resident NKT cells.

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+CD1a?CD5? or CD34+CD7+CD1a?CD5+ and are derived from human hematopoietic stem cells, embryonic stem cells and induced pluripotent stem cells b\ 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: The invention provides a method of obtaining a population of antigen-specific T cells from peripheral blood of a host. An embodiment of the method of the invention comprises (i) dividing PBMCs from peripheral blood of a host into more than one sub-population; (ii) contacting the PBMCs with an antigen and IL-2; (iii) obtaining a sample of PBMCs from each sub-population; (iv) identifying an antigen-reactive sub-population by determining by high throughput quantitative PCR the expression of a factor produced by the PBMCs of each sample; (v) dividing the antigen-reactive sub-population into microcultures; (vi) identifying the antigen-reactive microculture; and (vii) expanding the microculture, thereby obtaining a population of T cells specific for the antigen. The invention also provides a population of T cells obtained by the inventive method, a pharmaceutical composition comprising the same, and a method of treating a disease in a host using the pharmaceutical composition.

Abstract: A method of enriching stem or progenitor cells that includes growing a heterogeneous cell sample comprising stem and/or progenitor cells on a first substrate that is hydrophobic and has an elastic modulus less than about 100 MPa; recovering the heterogeneous cell sample from the first substrate; growing the recovered heterogeneous cell sample on a second substrate that is hydrophilic and has an elastic modulus higher than the elastic modulus of the first substrate to produce a subpopulation of nonadherent cells and a subpopulation of adherent cells; and recovering the nonadherent cell subpopulation, which is enriched for stem and/or progenitor cells.

Abstract: The present invention relates to a polypeptide binding to a chymase (EC 3, 4, 21,39), wherein the polypeptide comprises or consists of an amino acid sequence selected from the group consisting of: (a) GVTLFVALYDY(X1)A(X2)(X3)(X4)(X5) (X6)LSFHKGEKFQIL(X7 (X8)(X9)(X10) (X11)(X12)G(X13)(X14)WEARSLTTGETGYIPSNYVAPVDSIQ (SEQ ID NO: 1), wherein (X1) is R, N, Q, E, K, H, S, T, C, or D; (X2) is E, T, D, Q, L, P, A, S, C, M, N, E, G, A, V or I; (X3) is R, T, H, N, K, S, C, N or Q; (X4) is S, W, T, C, N, Q, For Y; (X5) is T, H, L, F, C, S, M, N, Q, R, K, G, A, V, I, P, Y or W; (X6) is D, Q, H, E, S, T, C, N, R or K; (X7) is D, N, R, E, Q, S, T, C, K or D; (X8) is M, W, G, F, A, S, T, C, S, N, Q, Y, V, L, I or P; (X9) is T, H, S, D, C, N, Q, R, K, E or absent; (X10) is V, T, Q, G, A, L, I, P, S, C, M, N or absent; (X11) is P, A, D, G, K, V, L, I, E, R, M, H or absent; (X12) is N, V, P, I, E, T, S, A, G, L, C, M, Q or D; (X13) is D, E, T, P, G, A, V, L, I, S, C, M, N or Q, and (X14) is W, Y, L, G, A, V, I, P, M, or F; (b)

Abstract: A method of expanding hematopoietic stem cells. Also disclosed is a method of diagnosing primary or secondary bone marrow failure syndrome. The invention further includes a method of treating primary or secondary bone marrow failure syndrome.

Abstract: The present invention relates to a method for preparing a cytotoxic lymphocyte characterized in that the method comprises the step of carrying out at least one of induction, maintenance and expansion of a cytotoxic lymphocyte in the presence of fibronectin, a fragment thereof or a mixture thereof.

Abstract: Methods for inducing, expanding, and/or generating alloantigen-specific regulatory T cells. Alloantigen-specific regulatory T cells can be induced, expanded, and/or generated from naive CD4+CD25? T cells by using CD40-activated B cells. The regulatory T cells can be human T cells. In one embodiment, the alloantigen-specific human regulatory T cells can be CD4highCD25+Foxp3+ regulatory T cells.

Abstract: A method for the in vitro production of a cell population P? from a cell population P, the production requiring the presence of at least one factor which is expressed by feeder cells, wherein a) feeder cells proliferate at a temperature T1, b) proliferated feeder cells are contacted with the cell population P, c) the cell mixture obtained at step (b) is cultivated at a temperature T2 which is chosen such that the cell population P proliferates and the feeder cells do not proliferate, the at least one factor being expressed by the feeder cells, and d) the cell population P? so produced is recovered. Advantageously, the production consists in an expansion, the feeder cells are insect feeder cells and the cell population P to be expanded is a T lymphocyte population, preferably a Trl lymphocyte population.

Abstract: The invention relates to the use of notch regulators for modulating IL-22 production in T-cells, by influencing the activity or activation of the notch signal path. The invention further relates to the use of modulating the immune response, primarily in case of infection reactions. The invention in particular relates to the use for treating illnesses associated with infections. The invention further relates to the use for reducing IL-22 production in T-cells.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.

Abstract: The present invention relates to methods for preparing an artificial immune system. The artificial immune system comprises a cell culture comprising T cells, B cells and antigen-primed dendritic cells. The artificial immune system of the present invention can be used for in vitro testing of vaccines, adjuvants, immunotherapy candidates, cosmetics, drugs, biologics and other chemicals.

Abstract: The present invention relates to cell labeling and imaging using a multifunctional perfluorocarbon (PFC) nanoemulsion. In particular, the perfluorocarbon nanoemulsion containing optical nanoparticle is provided with both optical characteristics and 19F magnetic resonance characteristics, thus can be used for magnetic resonance imaging (MRI) and optical imaging (OI) simultaneously. Cell labeling and imaging using the perfluorocarbon nanoemulsion containing quantum dot nanoparticle exerted no effect on cell viability. Therefore, perfluorocarbon nanoemulsion can be applied to methods for multifunctional and effectively cell labeling and imaging.

Abstract: The present invention provides methods and compositions for treating chronic inflammatory disease in a subject and associated pharmaceutical compositions, medical devices and systems.

Abstract: A method for generating/expanding in vitro a CD4+CD25+ T regulatory (Tr) cell and the use thereof in the treatment of diseases associated with a cell-mediated immune response (including T- and antibody-mediated responses).

Abstract: A method of manipulating allogeneic cells for use in allogeneic cell therapy providing a composition of highly activated allogeneic T-cells which are infused into immunocompetent cancer patients to elicit a novel anti-tumor immune mechanism, or “Mirror Effect”. In contrast to current allogeneic cell therapy protocols where T-cells in the graft mediate the beneficial graft vs. tumor (GVT) and detrimental graft vs. host (GVH) effects, the allogeneic cells of the present invention stimulate host T-cells to mediate the “mirror” of these effects. The mirror of the GVT effect is the host vs. tumor (HVT) effect. The “mirror” of the GVH effect is the host vs. graft (HVG) effect. The anti-tumor HVT effect occurs in conjunction with a non-toxic HVG rejection effect. The highly activated allogeneic cells of the invention can be used to stimulate host immunity in a complete HLA mis-matched setting in a patient.

Abstract: The present invention provides a method for activating a Natural Killer (NK) cell by contacting the NK cell in vitro with an activating tumour cell preparation (ATCP). The invention also provides an activated NK cell produced by such a method and its use in the treatment of cancer.

Abstract: Methods for inducing, expanding, and/or generating alloantigen-specific regulatory T cells. Alloantigen-specific regulatory T cells can be induced, expanded, and/or generated from naive CD4+CD25? T cells by using CD40-activated B cells. The regulatory T cells can be human T cells. In one embodiment, the alloantigen-specific human regulatory T cells can be CD4highCD25+Foxp3+ regulatory T cells.

Abstract: Carbon nanotube (CNT)-based compositions for activating cellular immune responses are provided. The CNTs function as high surface area scaffolds for the attachment of T cell ligands and/or antigens. The CNT compositions function as artificial antigen-presenting cells (aAPCs) or as modular vaccines. The disclosed CNT aAPCs are efficient at activating T cells and may be used to activate T cells ex vivo or in vivo for adoptive or active immunotherapy.

Abstract: The present invention relates a combination for use in the treatment and/or prevention of mastitis containing i) an agonistic anti-CD40 monoclonal antibody or a CD40 ligand or a vector coding for the anti-CD40 antibody or a vector coding for the CD40L; and ii) inactivated or attenuated bacteria selected from the group consisting of Staphylococcus, Streptococcus, Listeria or Escherichia.

Abstract: Disclosed are compositions and methods related to rendering ineffective Th1 T cells resistant to the inhibitory cytokine milieu present in a cancer microenvironment. Tumor-specific T cells are modified to employ a chimeric receptor that binds inhibitory/suppressive cytokines and converts their intracellular consequences to a Th1 immunostimulatory/activating signal. The T cells employ a chimeric antigen receptor having exodomains for IL10, IL13 and/or IL4 fused with the signal transducing endodomains for IL2 and/or IL7.

Abstract: A method of regulatory cell therapy for a treating a patient in need thereof, wherein 104 to 106 regulatory T cells are administrated to the patient.

Abstract: The present invention includes a composition and a method of making the same comprising a non-transformed, immortalized T-lymphocyte cell-line, wherein the T lymphocytes are IL-2 dependent and interact with an extracellular matrix.

Abstract: 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.

Abstract: The invention provides CD4+CD25? T cells and Tr1-like regulatory T cells (i.e., contact-independent Type 1-like regulatory T cells), processes for their production and their use for regulatory purposes.

Abstract: Provided are methods for treating a NAD comprising administering to a patient suffering from a NAD a composition comprising an eIF5A inhibitor compound in an amount effective to prevent intracellular hypusination of eIF5A, whereby gene expression of NMD-susceptible mRNA is increased.

Abstract: A method of increasing immunological effect in a patient by administering an effective amount of a primary cell derived biologic to the patient, inducing immune production, blocking immune destruction, and increasing immunological effect in the patient. Methods of treating an immune target, treating a tumor, immune prophylaxis, and preventing tumor escape.

Abstract: Provided herein are compositions and methods of preparing therapeutic cytotoxic T cells. In certain embodiments, such T cells are generated through activation of donor cells by patient stimulator cells.

Abstract: The present invention provides compositions and methods for treating cancer in a human. The invention includes relates to administering a genetically modified T cell to express a CAR wherein the CAR comprises an antigen binding domain, a transmembrane domain, a costimulatory signaling region, and a CD3 zeta signaling domain.