Abstract: An object of the present invention is to provide a method of efficiently constructing a library abundant in diversity and also usable for screening of a compound that binds to a target substance having protease activity. The present invention provides a method of constructing an azoline compound library containing two or more azoline compounds having an azoline backbone introduced into at least one of Cys, Ser, Thr, and 2,3-diamino acid, and analogs thereof of Xaa0 of a peptide represented by the following formula (I): A-(Xaa0)n-B??(I) [wherein, m numbers of Xaa0s respectively represent arbitrary amino acids, at least one of which is an amino acid selected from the group consisting of Cys, Ser, Thr, and 2,3-diamino acid, and analogs thereof, m represents an inter selected from 2 to 40, and A and B each independently represent a peptide composed of from 0 to 100 amino acids].

Abstract: The present invention provides a method of making a proteinase-engineered cancer vaccine for treating a cancer patient, especially for cancer patient at advanced/metastatic stage. The cancer vaccine comprises dead cancer cells with unbroken plasma membrane wherein the extracellular proteins and extracellular portion of membrane proteins are cleaved by proteinase digestion. The cancer vaccine may be derived from cancer cell lines or patients' cancer cells. The present invention provides a method of treating a cancer patient by administrating an effective amount of the cancer vaccine to the patient. In a clinical trial with 35 cancer patients, the cancer vaccine therapy brings cancer-free lives (no detectable tumor, micro tumor or cancer cells after treatment) back to 40% of these patients. The cancer vaccine therapy for the first time brings the promise of cure to this deadly disease.

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 present invention provides recombinant proteins comprising the amino acid sequence of an intracellular segment of CD40 and an amino acid sequence mediating the association of the recombinant protein with the constant region of an immunoglobulin heavy chain. The recombinant proteins according to the present invention are useful for inducing clonal expansion of a B cell having a predetermined antigen-specificity without the need for T cell or CD40L mediated co-stimulation. Thus, the present invention provides tools for clonal expansion of B cells specific for an antigen of interest and the production of B cells secreting antibodies specific for an antigen of interest. The recombinant proteins of the present invention may also be used for generating fully human monoclonal antibodies with a predetermined antigen-specificity from the B cell repertoire of a human subject.

Abstract: The invention relates to a porous material for body fluid treatment for promoting lymphocyte proliferation in lymphocyte culture which contains a high-molecular compound having an angle of contact with water within the range of 40 to 98°, and a porous material for body fluid treatment which comprises activated carbon; and also relates to a treatment device wherein the porous material is used; a method for proliferating lymphocytes; a method for producing mammalian lymphocytes; a method for producing a pharmaceutical composition; an additive body fluid to be added to a culture medium on the occasion of lymphocyte culture; a method for treating a disease against which a therapeutic effect is produced by returning extracorporeally activated mammalian lymphocytes into the body; and a method of manufacturing the porous materials for body fluid treatment for promoting the lymphocyte proliferation in lymphocyte culture.

Abstract: A method of treating cancer in a patient comprises immortalizing B cells collected from the patient by infection with Epstein Barr virus, transforming the cells to a latent stage, culturing the cells in the presence of a cancer antigen, harvesting exosomes released from the cells, administering the exosomes to the patient. Alternatively the harvested exosomes are loaded with cancer antigen.

Abstract: Techniques are provided for allowing a user to create a document processing job (e.g., a print job, a scan job, a copy job, fax job) at a mobile device instead of at a document processing device, such as a printer, scanner, or copier. A cloud service interacts with the mobile device to retrieve job settings data from the mobile device. The cloud service generates a job identifier, associates the job identifier with job settings associated with the job settings data, and sends the job identifier to the mobile device, which displays the job identifier to the user. The user later enters the job identifier at the document processing device, which, in turn, uses the job identifier to request the job settings from the cloud service. The cloud service identifies the job settings based on the job identifier and sends the job settings to the document processing device.

Abstract: The present invention relates to chimieric or humanized antibodies derived from the mouse monoclonal antibody HH1. The applications of the present invention include therapeutic applications in which pharmaceutical compositions comprising the antibodies of the present invention or radioimmunoconjugates hereof are used for treating B-cell malignancies.

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: The present invention relates to humanized antibodies or fragments thereof that bind to human CD19. More specifically, the present invention relates to a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32.

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: 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: Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.

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 present invention provides simple and rapid methods for measuring the function of a desired subset of lymphocytes, for example, T cells, B cells or NK cells. In addition, the present invention provides an all-in-one kit that contains reagents which permit a rapid and reliable analysis of the functions of T cells, B cells and NK cells obtained directly from whole blood or cord blood.

Abstract: This application relates to an in vitro method of producing a polyclonal IgG preparation. The method comprises (i) placing a polyclonal B-cell population enriched in IgG-secreting B cells in a culture medium; and (ii) culturing the polyclonal B-cell population under conditions enabling the production of the polyclonal IgG preparation from the polyclonal B-cell population. This improved method enables the production of antibodies (preferably IgG) and facilitates long-term culture of polyclonal B-cell populations.

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 the insertion of a promoter sequence from an MHC class I gene promoter into a lentiviral vector in order to direct the transcription of a transgene, which preferably encodes an immunogenic polypeptide to be expressed in a mammalian cell host, preferably APC (DCs). The invention encompasses these vectors, methods of making the vectors, and methods of using them, including medicinal uses.

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 generally to systems and methods of enhancing recovery of function of injured tissue through administration of a composition comprising a relatively pure populations of B lymphocyte cells in a pharmaceutically acceptable carrier to the injured tissue. Kits are provided to aid in purification of B cells from heterogeneous mixtures of cells and administration of B cells to injured tissue.

Abstract: The invention discloses a method of prenatal diagnosis comprising the step of isolating exosomes from an isolated fluid, wherein the exosomes are identified by biomarker detection. Furthermore, the invention discloses the isolation of exosomes from an isolated fluid and the use of a biomarker, particularly CD24 to isolate exosomes from an isolated fluid.

Abstract: The present invention provides a blood analyzer and a blood analyzing method capable of obtaining information regarding B lymphocytes and T lymphocytes without using a fluorescence-labeled antibody. The blood analyzer of the present invention includes a blood specimen supplying portion, a sample preparation portion that prepares a measurement sample without using a fluorescence-labeled antibody by mixing a blood specimen supplied from the blood specimen supplying portion, a hemolyzing agent, and a fluorescent dye that stains nucleic acid, a light source, a first detector that detects fluorescence, a second detector that detects scattered light, and information processing portion that classifies lymphocytes based on the intensity of fluorescence and scattered light, and based on the fluorescence intensity of the classified lymphocytes, obtains information regarding B-lymphocytes and T-lymphocytes.

Abstract: The invention relates to a modified lymphoid cell having gene conversion fully or partially replaced by hypermutation, wherein said cell has no deleterious mutations in genes encoding paralogues and analogues of the RAD51 protein, and wherein said cell is capable of directed and selective genetic diversification of a target nucleic acid by hypermutation or a combination of hypermutation and gene conversion. The invention also relates to a method for diversifying any transgenic target gene in said cell. Preferably, the target gene is integrated into the immunoglobulin light or heavy chain locus by targeted integration.

Abstract: The invention relates to methods to identify new SLC41A1 functions at the cell, tissue, organ and organism level. In part, it is related to methods useful in (a) identifying molecules that bind SLC41A1 polypeptides, which (b) modulate SLC41A1 related Na+/Mg2+ exchanger activity or its cellular or tissue specific expression. Thus, the invention comprises SLC41A1 mutation libraries, SLC41A1 specific antibodies, their generation and finding as well as an inducible conditional SLC41A1 knock out mice model and inducible conditional knock out SLC41A1 cell lines.

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: A microwell array chip that has multiple microwells and is employed to contain a single lymphocyte specimen in each microwell and detect antigen-specific lymphocytes in single units; wherein the microwell array chip is of a shape and of dimensions where only one lymphocyte is contained in each microwell. A method of detecting antigen-specific lymphocytes comprising the steps of adding antigen to each microwell in the above microwell array chip, stimulating the lymphocyte specimen, and detecting lymphocyte specimens reacting with the antigen.

Abstract: The present invention provides novel chimeric receptors and methods of screening using the chimeric receptors. The chimeric receptors comprise an extracellular domain of a tumor necrosis factor receptor superfamily (TNFRSF) receptor and an intracellular domain with kinase activity stemming from a receptor tyrosine kinase. According to an embodiment, the chimeric receptor comprises a full-length TNFRSF receptor. The present invention provides means for screening and testing of modulators of TNFRSF receptors.

Abstract: The invention provides a method for stimulating an immune response by administering to a lymphoid tissue a nucleic acid molecule comprising an expression element operationally linked to a nucleic acid sequence encoding one or more heterologous epitopes. The heterologous epitope can be inserted into a complementarity-determining region of an immunoglobulin molecule. The invention also provides a nucleic acid molecule comprising a hematopoietic expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide. The invention additionally provides a method of treating a condition by administering a nucleic acid molecule comprising a hematopoietic cell expression element operationally linked to a nucleic acid sequence encoding a heterologous polypeptide, wherein the nucleic acid molecule is targeted to a hematopoietic cell.

Abstract: Compositions and methods of therapy for treating diseases mediated by stimulation of CD40 signaling on CD40-expressing cells are provided. The methods comprise administering a therapeutically effective amount of an antagonist anti-CD40 antibody or antigen-binding fragment thereof to a patient in need thereof. The antagonist anti-CD40 antibody or antigen-binding fragment thereof is free of significant agonist activity, but exhibits antagonist activity when the antibody binds a CD40 antigen on a human CD40-expressing cell. Antagonist activity of the anti-CD40 antibody or antigen-binding fragment thereof beneficially inhibits proliferation and/or differentiation of human CD40-expressing cells, such as B cells.

Abstract: The present Invention provides novel methods for immortalizing cells that secrete antibodies of one or more specific isotypes. Polyclonal, oligoclonal, and monoclonal populations of cells obtained using the methods of the Invention can be screened on the basis of the functional and/or binding activities of the antibodies they secrete, for example directed to antigens of human or viral origin having medical interest, in cell culture conditions. Using these methods, human B cells that secrete antibodies binding human Cytomegalovirus, Herpes Simplex Virus, or HSP60 protein have been efficiently immortalized with Epstein-Barr virus.

Abstract: The invention provides a natural killer cell, NK-92, modified to express an Fc receptor on the surface of the cell, such as CD16 (Fc?RIII-A), or other Fc? or Fc receptors. The modified NK-92 cell can be further modified to concurrently express an associated accessory signaling protein, such as Fc?RI-?, TCR-?, or to concurrently express interleukin-2 (IL-2) or other cytokines. Additional methods are disclosed for various assays, assessments, and therapeutic treatments with the modified NK-92 cells.

Abstract: The invention relates to immunogenic conjugates comprising an immunogenic region of human papilloma virus E7 protein and the fibronectin EDA region, as well to compositions comprising said conjugates and to dendritic cells obtained by stimulation with said conjugates and compositions. Moreover, the invention relates to methods for the treatment of diseases caused by the human papilloma virus (HPV) using said conjugates, compositions and dendritic cells.

Abstract: The present invention provides recombinant proteins comprising the amino acid sequence of an intracellular segment of CD40 and an amino acid sequence mediating the association of the recombinant protein with the constant region of an immunoglobulin heavy chain. The recombinant proteins according to the present invention are useful for inducing clonal expansion of a B cell having a predetermined antigen-specificity without the need for T cell or CD40L mediated co-stimulation. Thus, the present invention provides tools for clonal expansion of B cells specific for an antigen of interest and the production of B cells secreting antibodies specific for an antigen of interest. The recombinant proteins of the present invention may also be used for generating fully human monoclonal antibodies with a predetermined antigen-specificity from the B cell repertoire of a human subject.

Abstract: The preparation and characterization of antibodies that bind to antigens on CLL or other cancer cells, especially to antigens upregulated in the cancer cells, and the identification and characterization of antigens present on or upregulated by cancer cells are useful in studying and treating cancer.

Abstract: A molecular delivery system including a plurality of nanowires (e.g., Si NWs), each of the nanowires having a surface layer formed of a silicon-containing material and a covalently bound linker (e.g., silane linker) attached to the surface layer and optionally including a substrate to which the nanowires are adhered or a molecule to be delivered attached to the linker. Also disclosed is a method of delivering into a cell an exogenous molecule.

Abstract: The present disclosure relates to systems, methods and compositions for the generation of antibody-producing B cells in vitro. Some embodiments are related to an in vitro system for generating antibody-producing B cells from hematopoietic stem/progenitor cells (HSPCs).

Abstract: The invention provides relatively short immunogenic peptides, and biologically active variants thereof, associated with leukemia which elicit an immune response. Nucleic acids encoding the immunogenic peptides and antibodies specific for the peptides are also provided. The immunogenic peptides can be included in pharmaceutical compositions, such as cancer vaccines, and used for the treatment of cancer.

Abstract: The invention is directed to methods for optimizing glycan processing in organisms (and in particular, plants) so that a glycoprotein having complex type bi-antennary glycans and thus containing galactose residues on both arms and which are devoid of (or reduce in) xylose and fucose can be obtained. The invention is further directed to said glycoprotein obtained and host system comprising said protein.

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 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: A process for damaging and maintaining damage to the nucleic acids of pathogens such as white blood cells, bacteria and viruses which may be contained in blood or blood components. This process comprises adding to the blood or blood component containing pathogens an effective amount of riboflavin, and exposing the fluid to light of an appropriate wavelength to damage the nucleic acid of the pathogen and to substantially maintain the damage to the pathogenic nucleic acids to allow for subsequent transfusion into a recipient.

Abstract: According to the invention there is described a method for ex vivo immunization of humans and animals comprising the following steps of: a) isolating autologous tumor cells; b) treating the tumor cells to prevent the survival thereof following reinfusion; c) incubating the thus treated tumor cells with intact heterologous bispecific and/or trisepcific antibodies showing the following properties: ?—binding to a T cell; ?—binding to at least one antigen on a tumor cell; ?—binding, by their Fc portion (in the case of bispecific antibodies), or by a third specificity (in the case of trispecific antibodies) to Fc receptor-positive cells.

Abstract: It is an object of the present invention to provide an immunodeficient animal capable of generating human-derived lymphoid cells, a human-derived lymphoid cell, and a method for producing a human antigen-specific antibody. The means for solving the aforementioned object is: an immature immunodeficient mammal into which human-derived hematopoietic precursor cells have been transplanted, and which is able to generate said human-derived hematopoietic cells or immunocompetent cells; and a method for producing a human-derived antibody, which is characterized in that it comprises recovering immunocompetent cells from the above-described mammal, culturing the immunocompetent cells, and collecting a human-derived antibody from the obtained culture product.

Abstract: The present invention provides DNA encoding a TADG-15 protein as well as a TADG-15 protein. Also provided is a vector capable of expressing the DNA of the present invention adapted for expression in a recombinant cell and regulatory elements necessary for expression of the DNA in the cell. The present invention further provides for methods of inhibiting TADG-15 expression and/or protease activity, methods of detecting TADG-15 mRNA and/or protein and methods of screening for TADG-15 inhibitors. Additionally, the present invention provides for cell-specific targeting via TADG-15 and methods of vaccinating an individual against TADG-15. The methods described are useful in the diagnosis, treatment and prevention of cancer, particularly breast and ovarian cancer.

Abstract: A process for damaging and maintaining damage to the nucleic acids of pathogens such as white blood cells, bacteria and viruses which may be contained in blood or blood components. This process comprises adding to the blood or blood component containing pathogens an effective amount of riboflavin, and exposing the fluid to light of an appropriate wavelength to damage the nucleic acid of the pathogen and to substantially maintain the damage to the pathogenic nucleic acids to allow for subsequent transfusion into a recipient.

Abstract: This invention relates to new uses of anti-CD40 antibodies in the treatment of diseases or conditions associated with neoplastic B-cell growth in particular use of anti-CD40 antibodies in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). The invention is particularly useful for the treatment of patients who have previously been administered (i) CHOP, (ii) the chimeric anti-CD20 monoclonal antibody rituximab, or (iii) combination therapy with CHOP and rituximab.

Abstract: The present invention relates to the cloning, identification and characterization of the unique and entire genomic sequences encoding new porcine DC-SIGN and LSECtin proteins, including the novel nucleotide sequences of the full-length cDNA and genes of both pDC-SIGN gene and pLSECtin. Also provided are the nucleic acid molecules encoding newly discovered porcine ICAM-3 isoforms from porcine monocyte-derived dendritic cells and the use thereof. Specifically, the invention is drawn to an isolated nucleic acid molecule comprising a nucleotide sequence encoding one or more of porcine DC-SIGN, porcine ICAM-3, porcine LSECtin, a complement of the nucleotide sequence or a functional, defined portion of the nucleotide sequence or a protein fusion product linked to a protein that may be of porcine or human origin.

Abstract: A method of increasing insulin content in adult islet beta cells is disclosed. The method comprises contacting the adult islet beta cells with an agent capable of down-regulating activity and/or expression of at least one component participating in a NOTCH pathway, the component being up-regulated in beta cell dedifferentiation above a predetermined threshold, thereby increasing the insulin content in adult islet beta cells. Methods of labeling dedifferentiated adult islet beta cells are also disclosed. Cell populations generated using the methods of the present invention and uses thereof are also disclosed.

Abstract: The present invention relates to humanized antibodies or fragments thereof that bind to human CD19. More specifically, the present invention relates to a humanized antibody or fragment thereof that binds to human CD19 comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, and/or a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and/or a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; and/or comprising a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, and/or a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 31 and/or a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 32.

Abstract: The present invention provides compositions and methods of controlling the direction and/or movement of migratory cells. Specifically, the invention is directed to the identification of novel chemorepellents and unimodal fugetaxins, their agonists and antagonists which alter or affect the movement of cells involved in immune, inflammatory or cancerous phenotypes.