Abstract: Nucleic acids encoding a chimeric or fusion polypeptide which polypeptide comprises a first domain comprising a translocation polypeptide; and a second domain comprising at least one antigenic peptide are disclosed. The preferred translocation polypeptide is a bacterial toxin translocation polypeptide, such as domain II of Pseudomonas aeruginosa exotoxin A (ETA(dII)). Such nucleic acids, expression vectors thereof, and cells expressing these vectors are used as vaccine compositions in a method for enhancing an antigen specific immune response, a method of increasing the numbers of CD8+ CTLs specific for a selected desired antigen in a subject, or a method of inhibiting the growth of a tumor in a subject.

Abstract: Isolated regulatory B cells are disclosed, and compositions including these isolated regulatory B cells. The isolated regulatory B cells are mammalian and express T cell immunoglobulin mucin-1 (TIM-1). In some embodiments the regulatory B cells produce IL-10. Methods for treating a subject with an immune-mediated disorder are disclosed. These methods include administering to the subject a therapeutically effective amount of a composition including regulatory B cells, thereby treating the immune mediated disorder in the subject. Methods are also disclosed for treating a subject with an immune-mediated disorder, wherein the methods include administering to the subject a therapeutically effective amount of an antibody that specifically binds TIM-1, wherein the antibody is activates TIM-1+CD19+ B cells. Methods are also disclosed for assessing the immune status of a subject.

Abstract: The invention provides a peptide comprising a human cytolytic T lymphocyte (CTL) epitope from the human tumor-associated antigen (TAA) New Gene Expressed in Prostate (NGEP), which can be used in vaccine prevention or therapy of prostate 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: 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: A novel cell type has been generated that has both Th1 characteristics and cytolytic activity. These Th1/killer cells are CD4+ cells purified from peripheral blood and manipulated to have Th1 characteristics such as production of IFN-gamma combined with cytolytic activity similar to cytotoxic T-cells (CTL). The CTL activity is targeted toward diseased cells, not normal cells. The cytolytic activity of the Th1/killer cells is mediated by Granzyme B-Perforin mechanism and results in apoptotic death of diseased cells. Methods of producing and using these Th1/killer cells include isolating CD4+ cells from peripheral blood, activating the CD4+ T-cells to form Th1/killer cells and administering these Th1/killer cells with the cytolytic activity to a patient wherein the Th1/killer cells are allogeneic to the patient.

Abstract: The present invention relates generally to the treatment of PML by infusion of activated and expanded autologous lymphocytes.

Abstract: A T cell receptor (TCR) having the property of binding to EVDPIGHLY HLA-A1 complex and comprising a specified wild type TCR which has specific mutations in the TCR alpha variable domain and/or the TCR beta variable domain to increase affinity. Such TCRs are useful for adoptive therapy.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from urinary bladder cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a tumour in the bladder or a metastasis arising from a tumour in the bladder. The method provides a new effective method for treating urinary bladder cancer and metastatic bladder cancer, without adverse side effects associated with the known treatments.

Abstract: Implantable pliable bone blocks comprising a solid block of cortical bone characterized by a length, width and thickness, having a first and a second face on opposite sides of the block. The first and second faces have a plurality slot features. The angle of incidence of the slot features of the first face and the x-axis and the angle of incidence of the slot features of the second face and the x-axis (a2) are such that the slots would intersect if they were in the same plane. Methods are provided for making implantable pliable bone blocks.

Abstract: The present invention provides an effective method for the transfection of dendritic cells by non-viral methods. The present invention provides this benefit by incubating dendritic cells and a specified transfection agent. The transfection agent comprises a polynucleotide and microparticles, with the microparticles being comprised of biodegradable polymer and cationic detergent. The dendritic cells and transfection agent are incubated for a time sufficient to transfect the dendritic cells with the polynucleotide.

Abstract: The invention provides methods of using isolated monocyte populations to treat subjects suffering from various ocular vascular disease or ocular degenerative disorders. The present invention also provides novel methods for isolating substantially pure monocyte populations. The methods involve extracting a blood sample or a bone marrow sample from a subject, debulking red blood cells from the sample, and then separating remaining red blood cells and other cell types in the sample from monocytes. Instead of using any selection or labeling agents, the red blood cells and other cell types are separated from monocytes based on their size, granularity or density. The isolated monocytes can be further activated in vitro or ex vivo prior to being administered to a subject. Isolated cell populations containing substantially pure CD14+/CD33+ monocytes are also provided in the invention.

Abstract: Described are methods, cell growth substrates, and devices that are useful in preparing cell-containing graft materials for administration to patients. Tubular passages can be defined in cell growth substrates to promote distribution of cells into the substrates. Also described are methods and devices for preparing cell-seeded graft compositions, methods and devices for preconditioning cell growth substrates prior to application of cells, and cell seeded grafts having novel substrates, and uses thereof.

Abstract: Methods and compositions for modifying glycans (e.g., glycans expressed on the surface of live cells or cell particles) are provided herein.

Abstract: The present invention relates to a composition for differentiating natural killer cells comprising osteopontin (OPN) as an active ingredient and a method for differentiation using the same. More precisely, osteopontin of the present invention accelerates differentiation of natural killer cells from hematopoietic stem cells and increases cytotoxic activity of natural killer cells, so that it can be effectively used as a composition for differentiating natural killer cells. OPN of the present invention regulates differentiation of natural killer cells capable of killing cancer cells, so that it can be effectively used for the treatment of cancer.

Abstract: The invention relates to a method of treating tumor cells within a patient wherein immature dendritic cells developed from the patient's monocyte cells and a lymphocyte cultured medium (LCM) adjuvant are introduced into the patient directly into the patient's tumor cells. The immature dendritic cells and LCM adjuvant combine with the antigens in the tumor cells to form a cancer vaccine, thereby immediately treating the tumor cells of the patient. The invention also provides a precursor treatment step of treating the patient with radiation therapy or a chemotherapy regimen.

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: Adoptive immune cells obtained by a method including (a) obtaining mammalian antigen-presenting associated cells; (b) culturing the resulting cells from step (a) in a culture liquid contained in a culture vessel coated with a sugar chain-containing polymer; and (c) detaching the cells from step (b) by shaking the culture vessel without treating the cells with an enzyme and without using a cell detaching tool. A method for treating a malignant tumor, type I diabetes, an atopic allergic disease or an infection, by administering the adoptive immune cells to a patient. A pharmaceutical composition for treating a malignant tumor, type I diabetes, an atopic allergic disease or an infection, including the adoptive immune cells and a pharmaceutically acceptable carrier.

Abstract: Disclosed are methods of isolating and using a population of FOXP3+ regulatory T cells in a variety of preventative and therapeutic approaches to autoimmune diseases, graft-versus-host disease and transplant rejection.

Abstract: The invention provides compositions and methods for delivering agents to localized regions, tissues, or organs in vivo by conjugating agent-loaded nanoparticles to cells having homing capability. The agents may be therapeutic or diagnostic agents such as cancer chemotherapeutic agents and imaging agents respectively.

Abstract: The present invention refers to a method of treating tumor growth and metastasis in a mammal, the treating comprising administering allogeneic effector cells together with trifunctional bispecific or trispecific antibodies or a combination thereof having the following properties: a) binding to a T cell b) binding to at least one antigen on a tumor cell c) binding via their Fc portion in the case of trifunctional bispecific antibodies or via third specificity in the case of trispecific antibodies to Fc receptor positive cells; the antibodies redirecting the allogenic cells away from host tissues in order to substantially reduce or avoid a graft versus host disease.

Abstract: Antigen specific regulatory T cells are described and related compositions, methods and systems. Methods to generate an antigen specific anti-inflammatory regulatory T cell is provided, the method comprising contacting either a T cell or an antigen presenting cell with a zwitterionic polysaccharide conjugated to the antigen for a time and under condition to generate an antigen specific regulatory T cell that is capable of inhibiting a pro-inflammatory response against the antigen.

Abstract: Provided herein are methods of suppressing tumor cell proliferation, of treating individuals having cancer or a viral infection, comprising contacting the tumor cells, or administering to the individual, placental perfusate, placental perfusate cells, or natural killer cells, e.g., placenta-derived intermediate natural killer cells, with an immunomodulatory compound or thalidomide.

Abstract: Immunostimulatory compositions and methods comprising an ITIM motif-containing DC immunoreceptor (DCIR) to mediate potent crosspresentation are described herein. The inventors evaluated human CD8+ T cell responses generated by targeting antigens to dendritic cells (DCs) through various lectin receptors. A single exposure to a low dose of anti-DCIR-antigen conjugate initiated antigen-specific CD8+ T cell immunity by all human DC subsets including ex vivo generated DCs, skin-isolated Langerhans cells and blood mDCs and pDCs. Enhanced specific CD8+ T cell responses were observed when antigens like, FluMP, MART-1, viral (HIV gag), etc. were delivered to the DCs via DCIR, compared to those induced by a free antigen, or antigen conjugated to a control mAb or delivered via DC-SIGN, another lectin receptor. Addition of Toll-like receptor (TLR) 7/8-agonist enhanced DCIR-mediated crosspresentation as well as crosspriming.

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 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 T cell receptor molecule (TCR) containing an alpha chain portion and a beta chain portion wherein the alpha chain portion contains three complementarily determining regions (CDRs): CDR1?: SSYSPS CDR2?: YTSAATL CDR3?: VVSPFSGGGADGLT or comprising or consisting of SPPSGGGADGLT and the beta chain portion contains three complementarity determining regions (CDRs): CDR1?: DFQATT CDR2?: SNEGSKA CDR3?: comprising SARDGGEG or comprising or consisting of RDGGEGSETQY, or wherein up to three amino acid residues in one or more CDRs are replaced by another amino acid residue. The invention also includes polynucleotides encoding the TCR molecules, and host cells containing the said polynucleotides. Patient derived T cells may have the polynucleotides encoding the TCR molecules introduced therein, and the engineered T cells may be introduced into the patient in order to combat a WT1-expressing malignancy.

Abstract: The present invention is directed to methods of identifying and enriching for viable Foxp3+ cells and the use of such cells. In particular, the present invention provides methods whereby viable Foxp3+ cells are isolated from a mixed population of cells; Foxp3+ cells being identifiable as those cells with relatively high forward scatter as assessed by a flow cytometer.

Abstract: A method for modifying access of cells to extravascular spaces and regions comprising administering to a patient an enzyme that cleaves chondroitin sulfate proteoglycans is provided. It has been found that administration of an enzyme that cleaves chondroitin sulfate proteoglycans to a patient disrupts extravasation of cells from the blood stream into tissue. The present invention provides methods of reducing penetration of cells associated with inflammation into tissue of a patient. Several methods are also provided for the regulation and suppression of inflammation comprising administering enzymes that digest chondroitin sulfates. Also provided are methods of treating and preventing inflammation associated with infection, injury and disease.

Abstract: The present invention provides T cell receptors (TCRs) having the property of binding to SLLMWITQC-HLA-A*0201, the SLLMWITQC peptide being derived from the NY-ESO-1 protein which is expressed by a range of tumour cells. The TCRs have a KD for the said that peptide-HLA complex of less than or equal to 1 ?M and/or have an off-rate (koff) of 1×10?3 S?1 or slower.

Abstract: The present invention relates to a biomaterial, specifically a hydrogel, formed from the extracellular matrix of the umbilical cord for its application in regenerative medicine. The invention particularly relates to a biomaterial made up of glycosaminoglycans isolated exclusively from the Wharton's jelly of the umbilical cord which can optionally contain cells, and also to the methods for the production and use thereof.

Abstract: The present invention relates to methods for the modulation of immune responses. More particularly, the invention relates to methods and uses of leptin for immune-modulation of the balance between the Th1/Th2 responses and for the treatment of immune-related disorders. Specifically, the methods of the invention comprise shifting the Th1/Th2 cell balance towards the proinflammatory state. This modulation of the cell balance may be performed by increasing the activity and/or the expression of leptin in a subject, for instance by raising the amount of leptin. The amount of leptin in a subject may be increased by activating immunoregulatory cells, or by administering an immunomodulatory amount of leptin or a homologue, derivative, or functional fragment of leptin.

Abstract: The present invention relates to a pharmaceutical preparation for treating an inflammatory condition, preferably a condition associated with ischemia comprising: a) a physiological solution comprising peripheral blood mononuclear cells (PBM-Cs) or a subset thereof, or b) a supernatant of the solution a), wherein the solution a) is obtainable by cultivating PBMCs or a subset thereof in a physiological solution free of PBMC-proliferating and PBMC-activating substances for at least 1 h.

Abstract: This invention relates to a natural killer cell line termed NK-92 and to NK-92 cell lines that have been modified by transfection with a vector to confer advantageous properties. The invention provides a modified NK-92 cell line that is transfected with a vector encoding a cytokine that promotes the growth of NK-92 cells. In a significant embodiment, the cytokine is interleukin 2. The invention additionally provides a modified NK-92 cell line that is transfected with a vector that expresses a thymidine kinase gene. The invention further provides a modified NK-92 cell line that is transfected with a vector that expresses a ?2 micrglobulin.

Abstract: The present invention relates to set overlapping immunogenic peptides of a variable antigen, and uses thereof, in particular for diagnostic and therapeutic purposes. The present invention relates also to a sub-population of CD8 T cells associated with the non-progressive status in HIV-infected subjects.

Abstract: The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising Mycobacterium tuberculosis antigenic peptides and uses there of.

Abstract: Provided are an iPS cell derived from a somatic cell such as an NKT cell, having the ?-chain region of the T cell antigen receptor gene rearranged to uniform V?-J? in an NKT cell receptor-specific way, NKT cells differentiated from the iPS cell, a method of creating the same, and an immune cell therapy agent prepared using cells differentiated from the iPS cell.

Abstract: Disclosed herein is a system and method for producing T cells from stem cell populations. Specifically exemplified herein is a culture system and method that produces CD4 cells and/or T cell subtypes from a CD4 lineage using a sample of hematopoietic stem cells. Adult hematopoietic precursor/stem cells (HPC) are progenitors to all lineages of immune cells. There has been limited success in generating functional CD4 T cells with this convenient culture system. Also disclosed herein is a novel stromal cell line expressing DL1, interleukin-7 (IL-7), and FMS-like tyrosine kinase 3 ligand (Flt3-L). This improved culture system can greatly facilitate the study of late T cell development and enables immunotherapeutic applications.

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 95 novel peptide sequences and their variants derived from HLA class I molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.

Abstract: First, to solve the problems of the present invention, the present inventors confirmed the presence of ovarian cancer antigen-specific T cells in the peripheral blood of ovarian cancer patients by using an experimental system that detects combinations of CD4 and IL-4 or IFN?. Next, using analogue peptides of the core protein MUC16 of the ovarian cancer-associated antibody C125, the present inventors revealed that antigen-specific CD4-positive T cells are present at an average frequency of about 4% in the peripheral mononuclear cells of patients and healthy subjects. Then, the present inventors analyzed the epitope for T cells in the core protein MUC16 of the ovarian cancer-associated antigen CA125, and determined the amino acid sequence FTLNFTITN (SEQ ID NO: 1) to be a shorter epitope. The present inventors further discovered that the analogue peptide OVCA11: GHTAPOPLLVPFTLNFTITN (SEQ ID NO: 11) is suitable for T cell activation.

Abstract: The present invention concerns the enhancement of immune response to microbial infection and/or inflammation-associated disease through at least partial inhibition of NLRC5. The inhibition may be of any suitable means, although in particular cases it is via siRNA agents. In specific embodiments, a particular domain of NLRC5 is targeted by the siRNA.

Abstract: A method of identifying an antigen-specific regulatory T cell (Treg) from a subject is discussed wherein the method comprises quantitatively or qualitatively detecting co-expression of each of cell markers CD4, CD25 and CD134, or alternatively, N each of cell markers CD8, CD25 and CD137, as well as one or more cell markers selected from the group of Treg cell markers consisting of CD39, CD73, CD127, CTLA-4 and Foxp3 on a cell in a suitable lymphocyte-containing sample from the subject in response to exposure to a target antigen. Also discussed are methods of isolating and expanding the identified antigen-specific Treg population, which may permit antigen-specific Treg cell therapy.

Abstract: Peptides or antibodies derived from alternative splice forms of proteins associated with a disease or physiologic condition are used as therapeutic or prophylactic agents. Peptides and antibodies derived from alternative splice forms of the vascular endothelial growth factor (VEGF) family of proteins are particularly useful in preventing or delaying the onset of tumors and inducing tumor regression.

Abstract: The invention provides compositions comprising activated marrow infiltrating lymphocytes, methods of generating populations of marrow infiltrating lymphocytes, uses of the marrow infiltrating lymphocytes of the invention, and a culture device for use in cell culture, for example for use in generating populations of activated marrow infiltrating lymphocytes. In certain embodiments, the marrow infiltrating lymphocytes can be used as a cancer therapeutic.

Abstract: The present invention refers to a method of producing immunosuppressive blood cells that can be used for the treatment of autoimmune diseases, in particular multiple sclerosis, organ graft rejection and graft-versus-host disease.

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: According to the present invention, peptides having the amino acid sequence of SEQ ID NOs: 14, 21, 23, 27, 36, 46, 57, 60 and 62 were demonstrated to have cytotoxic T lymphocyte (CTL) inducibility. Therefore, the present invention provides a peptide having the amino acid sequence selected from among SEQ ID NOs: 14, 21, 23, 27, 36, 46, 57, 60 and 62. The peptide can include one, two, or several amino acid substitutions, deletions, insertions, or additions so long as its CTL inducibility is retained. Furthermore, the present invention provides pharmaceutical agents for the treatment and/or prophylaxis of cancers, and/or prevention of postoperative recurrence thereof, which contain any of these peptides. Pharmaceutical agents of this invention include vaccines.

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

Abstract: The present invention relates to novel melanoma antigen peptides and specific T lymphocytes directed to said peptides and the use thereof for treating melanoma.

Abstract: The present invention discloses an immunotherapeutic method for treating patients suffering from colon cancer, by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more sentinel or metinel lymph nodes draining a tumour in the colon or a metastasis arising from a tumour in the colon. The present invention provides a new effective method for treating colon cancer and metastatic colon cancer, without adverse side effects associated with the known treatments.