Abstract: Provided are methods for treating inflammatory neurodegenerative diseases (e.g., multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease, Parkinson's disease, stroke/cerebral ischemia, head trauma, spinal cord injury, Huntington's disease, migraine, cerebral amyloid angiopathy, inflammatory neurodegenerative condition associated with AIDS, age-related cognitive decline; mild cognitive impairment and prion diseases in a mammal), or at least one symptom thereof in a subject by administering a therapeutic composition comprising at least one electrokinetically-altered fluids (e.g., electrokinetically-generated oxygen-enriched fluids) of the present invention. Particular aspects provide methods for inhibiting and/or modulating the function and/or activity of effector T-cells, and/or for cell-based tolerogenic therapy (e.g., by modulating development and/or function and/or activity of TREG cells and/or dendritic cells (DCs) and/or TH17 cells (e.g., ROR?t+ TH17 cells).

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

Abstract: The invention provides compounds and methods for the ex vivo or in vivo expansion of NK T cells, CD1d-reactive T cells, and J?Q+ T cells, and the modulation of their activities. These compounds and methods have diagnostic and therapeutic applications.

Abstract: A method of large scale expansion and simultaneous activation of NK cells and NK-like T cells in a closed cell culture system is presented, wherein the expanded cells exhibit increased cytotoxicity.

Abstract: The present invention provides an ex vivo method of treating plasmacytoid dendritic cells (pDC) in Th2- or Th17-associated diseases by modulating the cytokine expression or secretion using interferon lambda (IFN-?). For the Th-2 or Th17-associated diseases, pDC cells from a patient having the disease are exposed ex vivo with IFN-? in an effective amount to inhibit cytokine releases. The IFN-? exposed pDC are administered back into the patient. The present invention also provides a method of ex vivo IFN-? treatment of pDC, in conjunction with co-administration of a composition comprising IFN-?.

Abstract: The present disclosure relates to antigen specific tolerogenic antigen presenting cells presenting antigenic portions of an autoantigen and to related compositions, methods and systems.

Abstract: The invention provides nucleic acids comprising a nucleotide sequence encoding programmed death ligand-1 (PD-L1) and a nucleotide sequence encoding a fusion protein comprising thymidylate kinase (TMPK) or a variant thereof and a cell surface marker or a variant thereof. Recombinant expression vectors, host cells, populations of cells, pharmaceutical compositions, and kits relating to the nucleic acids are disclosed. Methods of treating or preventing a disease in a host and methods of suppressing an immune system in a host are also disclosed.

Abstract: An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and/or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal. Methods of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy are also provided.

Abstract: Provided are transplants and methods for augmenting formation and restoration of organ and tissue, for example, bone formation, by administering autologous or allogeneic human embryonic-like adult stem cells (ELA cells). Also provided is a method for augmenting formation of tissues and organs by administering a transplant having ELA stem cells or combination of ELA stem cells.

Abstract: This invention features methods of enhancing immune responses in mammalian subjects and in vitro methods of enhancing the response of a T cell. Also embodied by the invention are methods of receiving and preventing the induction of energy in T cells.

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 for the identification of an antigen surrogate to the native antigens for the autoimmune disease pemphigus vulgaris. Ligands are discovered using large random peptoid or cyclic peptoid libraries that are screened against known antibodies to autoimmune diseases. The ligands may be useful as drugs in the treatment of such diseases and can also be used in combination with the concomitant removal of T-cells associated with autoimmune disorders.

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

Abstract: Based upon a strong correlation between regulator T cells (Treg cells) and suppressing or preventing a cytotoxic T cell response, provided are methods for the production of ex vivo activated and culture-expanded isolated CD4+CD25+ suppressor Treg cells for the prevention or suppression of immune reactions in a host, particularly in a human host, and including autoimmune responses. The resulting ex vivo culture-expanded Treg cells provide a sufficient amount of otherwise low numbers of such cells, having long term suppressor capability to permit therapeutic uses, including the preventing, suppressing, blocking or inhibiting the rejection of transplanted tissue in a human or other animal host, or protecting against graft vs host disease. Also provided are therapeutic and immunosuppressive methods utilizing the ex vivo culture-expanded Treg cells for human treatment, and high efficiency methods for research use.

Abstract: Disclosed are cells, methods of modulating cells, and therapeutic uses of the cells for the immune modulation of mammals in need thereof. Immune modulation including alteration of cytokine profile, cytotoxic activity, antibody production and inflammatory states is achieved through the administration of various cell types that have been unmanipulated or manipulated in order to endow specific biological activity. Cellular subsets and administration of the subsets in combination with various agents are also provided. One embodiment teaches the previously unknown finding that adipose tissue derived mononuclear cells contain T cells with immune regulatory properties that alone or synergistically with various stem cells induce immune modulation upon administration. Another embodiment is the finding that stimulation of stem cell activation results in stem cell secondary activation of immune modulatory cells, one type which is T regulatory cells (Tregs).

Abstract: A method of modifying cells includes removing fluid including cells from a patient, contacting the removed fluid from the patient with at least one surface upon which at least one agent to interact at least one cell receptor is immobilized to modify cells in the fluid, and returning the fluid to the patient. The agent can, for example, be immobilized via covalent bonding or ionic bonding to the at least one surface. The fluid can, for example, be blood or a blood fraction. The agent can, for example, be an agonist, an antagonist or an inverse agonist.

Abstract: Methods are provided for suppressing the immune system response in recipients of transplanted organs, tissues or cells. An extracorporeal quantity of blood from the intended transplant recipient is treated to induce monocytes contained in the blood to differentiate and form dendritic cells. The maturation of the dendritic cells is truncated at a stage where the dendritic cells can inactivate T cell clones which would otherwise generate an undesired immune system response. The immature dendritic cells can be directly administered to the transplant recipient, or the dendritic cells can be co-incubated with the bone marrow or stem cell preparation, prior to transplantation, in order to suppress or eliminate anti-recipient donor T cells contaminating the bone marrow or stem cell preparation. The methods can be used to suppress graft versus host disease in recipients of transplanted bone marrow or stem cells, or to suppress rejection of transplanted organs or tissue.

Abstract: A method of determining if a subject's CD8+ T-cells functionally recognize an HLA-E/Hsp60sp target structure comprising a) contacting a sample of the subject's CD8+ T-cells with a HLA-E+ cell loaded with Hsp60sp, b) quantifying proliferation of the contacted HLA-E+ cell, c) contacting a sample of the subject's CD8+ T-cells with a HLA-E+ cell which is loaded with a peptide which does not bind to HLA-E, d) quantifying proliferation of the HLA-E+ cell loaded with the peptide which does not bind to HLA-E following contact with the subject's CD8+ T-cells, e) comparing the proliferation quantified in step d) with the proliferation quantified in step b)

Abstract: Methods and compositions are provided to augment the conversion of mixed hematopoietic cell chimerism to complete donor cell chimerism following allogeneic hematopoietic cell transplantation (HCT), where such transplantation may be utilized for treatment of cancer such as leukemia and lymphoma or for other conditions requiring reconstitution of the hematopoietic system, e.g. treatment of anemias, thalassemias, autoimmune conditions, and the like. The present invention improves on conventional DLI by utilizing a composition of substantially purified donor memory CD8+ T cells as DLI following allogeneic HCT, where the cells are administered at a suitable time following transplantation. The methods provide for a more complete donor chimerism, and have the further benefit of killing tumor cells without GVHD. The memory CD8+ T cells may include one or both of central and effector memory T cells, usually both.

Abstract: The present invention provides methods and compositions for affecting functional differences of blood memory CD4+ T cell populations in a subject by providing isolated and purified T cell subsets selected from X5+ CD4+ or X5? CD4+ T cells to a subject. Another invention includes a method for regulating CD4+ T cells comprising the steps of isolating and purifying one or more naïve CD4+ T cells from a subject; contacting the one or more naïve CD4+ T cells with one or more cytokines selected from IL-6 and TGF-b, IL-12, or TGF-b and IL-12; and modifying the expression of the factors from the naïve CD4+ T cells wherein the one or more factors are the expression of IL-21, the decreased expression of IFN-g, the expression of CXCR5, the expression of Bcl-6, the decreased expression of Blimp-1, or a combination thereof.

Abstract: Provided are peptide vaccines including the signal peptide domain of selected target antigens of intracellular pathogens. The peptide vaccines of the invention contain multiple class II and class I-restricted epitopes and are recognized and presented by the majority of the vaccinated human population. Further provided, in particular, are anti tuberculosis vaccines. Also further provided are compositions including the vaccines as well as their use to treat or prevent infection.

Abstract: The present invention discloses an immunotherapeutic method for treating a patient suffering from a disseminated cancer by administering expanded tumour-reactive CD4+ helper and/or CD8+ T-lymphocytes obtainable from one or more metastasis-draining lymph nodes (metinel nodes) draining a metastasis. The method comprises identification of one or more metinel lymph nodes in a patient, resection of the one or more nodes and, optionally all or part of the metastases, isolation of metastasis-reactive T-lymphocytes from said lymph nodes, in vitro expansion of said metastasis-reactive T-lymphocytes, and administration of the thus obtained T-lymphocytes to the patient, wherein the T-lymphocytes are CD4+ helper and/or CD8+ T-lymphocytes.

Abstract: Chimeric receptor genes suitable for endowing lymphocytes with antibody-type specificity include a first gene segment encoding a single-chain Fv domain of a specific antibody and a second gene segment encoding all or part of the transmembrane and cytoplasmic domains, and optionally the extracellular domain, of an immune cell-triggering molecule. The chimeric receptor gene, when transfected to immune cells, expresses the antibody-recognition site and the immune cell-triggering moiety into one continuous chain. The transformed lymphocytes are useful in therapeutic treatment methods.

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

Abstract: A conjugate protein comprising a GM-CSF or fragment thereof linked to an IL-21 or fragment thereof is described. The conjugate protein has unexpected immune activating and tumoricidal properties and is useful in a variety of therapeutic applications.

Abstract: The present invention relates to semi-allogeneic antigen-presenting cells into which proteins and/or peptides or RNA or DNA or cDNA, respectively, encoding said proteins and/or peptides which are overexpressed in tumor cells or which are derived from autologous tumor cells or different tumor cells or different tumor cell lines have been introduced. Furthermore the invention relates to methods for the generation of these semi-allogeneic antigen-presenting cells as well as to the use thereof in the treatment of tumor diseases.

Abstract: The present invention discloses an improved method for expansion and activation of tumor-reactive lymphocytes, in particular CD4+ helper and/or CD8+ T-lymphocytes, which may be used for treating and/or preventing cancer. The method provides high numbers of tumor-reactive T-lymphocytes within a short time span and the possibility of directing development of tumor-reactive CD4+ helper and/or CD8+ T-lymphocytes towards specific subpopulations. The method comprises a first phase of stimulating tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes with tumor-derived antigen together with at least one substance having agonistic activity towards the IL-2 receptor to promote survival of tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes; and a second phase of activating and promoting growth of tumor-reactive CD4+ T helper and/or CD8+ T-lymphocytes, wherein the second phase is initiated when the CD25 cell surface marker (or IL-2R marker) is down-regulated on CD4+ T helper and/or CD8+ T-lymphocytes.

Abstract: A conformable tissue implant is provided for use in repairing or augmenting a tissue defect or injury site. The tissue implant contains a tissue carrier matrix comprising a plurality of biocompatible, bioresorbable granules and at least one tissue fragment in association with the granules. The tissue fragment contains one or more viable cells that can migrate from the tissue and populate the tissue carrier matrix. Also provided is a method for injectably delivering the tissue implant.

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

Abstract: The present 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: The present invention discloses the protease stratum corneum chymotrytic enzyme (SCCE) is specifically over-expressed in ovarian and other malignancies. A number of SCCE peptides can induce immune responses to SCCE, thereby demonstrating the potential of these peptides in monitoring and the development of immunotherapies for ovarian and other malignancies.

Abstract: The present invention provides a method for treating a subject having chronic lymphocytic leukemia (CLL) comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the proliferative compartment of a CLL clone of the subject to treat chronic lymphocytic leukemia in the subject. The present invention also provides a method for treating a subject having chronic lymphocytic leukemia comprising administering to the subject one or more agents that target cell surface membrane antigens expressed preferentially on cells of the “resting re-entry compartment” to treat chronic lymphocytic leukemia in the subject.

Abstract: The present invention is related to the development and treatment of autoimmune disease. Autoimmune diseases can result from tissue damage caused by the activation of autoreactive T cells by autoantigens. For example, peptide fragments of naturally occurring proteins (i.e., for example, chromogranin A) may activate autoreactive T cells that result in the destruction of pancreatic ? islet cells, possibly by the release of inflammatory cytokines (i.e., for example, interferon-?). One naturally occurring biologically active chromogranin A peptide fragment, WE14, may comprise a diabetogenic autoantigen. Truncation and extension analysis of WE14 indicates that the stimulating binding register of WE14 occupies only half of the mouse IAg7 peptide binding groove, leaving positions p1 to p4 empty.

Abstract: The present invention provides compositions, methods, and systems for generating antigen-specific long-term memory T-cells using mTOR pathway inhibitors. The present invention provides compositions, systems, and methods for administering antigen-specific long-term memory T-cells to a subject (e.g., to a subject with cancer in adoptive transfer type of procedures).

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

Abstract: Disclosed are: a method for culture of disease antigen specific CTLs and ??T cells in one culture step conveniently and efficiently; and a pharmaceutical agent and a therapeutic/prophylactic method both of which use a cell produced by the method. Blood is collected and peripheral blood mononuclear cells are separated from the blood. Aminobisphosphonate and a disease antigen are added to the peripheral blood mononuclear cells at the beginning of culture, and the cell culture is carried out for a predetermined period to proliferate/induce disease antigen specific CTLs and ??T cells simultaneously until the numbers of the cells reach values that are effective for the treatment of a disease. The CTLs and the ??T cells thus produced are used for the treatment.

Abstract: A method of treating cancer comprises: (a) providing allogenic or autologous white blood cells from a suitable donor; and then (b) administering the white blood cells to the subject in an amount effective to treat the cancer. Preferably the white blood cells comprise innate immune cells. Preferably the white blood cells comprise less than 10% by number of cytotoxic T lymphocytes. Preferably the white blood cells, or more particularly the innate immune cells, are preselected in vitro to kill cancer cells in vitro (for example, by collecting white blood cells from the patient and determining that the white blood cells kill cancer cells in vitro before and thereby pre-selecting the donor, before collecting a subsequent population of cells from the donor for administration).

Abstract: Provided is a composition for in vivo transplantation for the treatment of human cervical cancer, comprising mononuclear cells derived from umbilical cord blood and a pharmaceutically acceptable carrier. When the umbilical cord blood-derived mononuclear cells are transplanted in vivo, cervical cancer can be effectively treated. In particular, the mononuclear cells derived from the umbilical cord blood retain high differentiation and proliferation abilities and exhibit very low graft-versus-host (GVH) reactions which are side effects caused by transplantation, and thus, can be transplanted to many patients.

Abstract: Fetal blood multi-lineage progenitor cells that are capable of a wide spectrum of transdifferentiation are described.

Abstract: The present invention provides an immunotherapeutic agent and immunotherapy allowing the extension of the survival time of patients with pancreatic cancer. The immunotherapy of the present invention is characterized by comprising the steps of culturing peripheral blood lymphocytes of a patient with pancreatic cancer by stimulating the lymphocytes with an anti-CD3 antibody and an anti-CD52 antibody, thereby to obtain an immunotherapeutic agent, and administering at least four infusions of the resultant immunotherapeutic agent to the same patient, wherein each of the infusions of the immunotherapeutic agent comprises at least 15×109 cells of activated lymphocytes, the percentage of CD3? CD56+ NK cells in the activated lymphocytes is at least 30%, and the administration of the immunotherapeutic agent is begun for the patient who is in at least one state of two or more particular immunocompromised states.

Abstract: The present invention relates to the discovery of novel methods of inducing a natural killer (NK) cell-mediated immune response and increasing NK activity in a mammal for the treatment of tumors and virus infections. The method comprises the steps of isolating peripheral blood mononuclear cells (PBMCs) from the subject, exposing the PBMCs in vitro to protein conjugate comprising granulocyte macrophage colony stimulating factor (GM-CSF) covalently linked to a soluble peptide antigen, under conditions effective to activate the PBMCs, and administering the activated PBMCs to the subject. The invention also relates to a method of detecting in a subject a cytotoxic NK cell-meditated immune response or NK cell activity in vitro by CD336 expression and/or lysis of the K562 tumor line. The invention further relates to a method for determining whether a subject has had a therapeutically effective response to a protein conjugate by assessing the NK activity of activated PBMCs from the subject.

Abstract: A composition comprising a glassified, stabilized particle preparation having a low water activity (between about 0.1 and 0.9) is provided. The preparations provide improved products with enhanced storage stability, less expensive cost of processing, and extended shelf life. The glassified, stabilized particle preparations are particularly efficacious in the preparation of perishable products, especially pharmaceutical agents, such as human blood and blood products (e.g., red blood cells). A single emulsion process comprising a 2-phase system for preserving food and pharmaceutical products is also provided. Stabilized biological products as glassified beads are also provided, as well as a method for rehydrating and/or reconstituting the glassified beads to provide useful and fully active reconstituted and/or rehydrated materials is also presented.

Abstract: Disclosed is a method to recover an antigen presenting cells (APCs) and immune cells rich mixture (AIM) from peripheral blood mononuclear cells (PBMC) mobilized with one or more cell adhesion inhibitors for the preparation of an AIM vaccine or an AIM adoptive immunotherapy preparation. In addition, AIM mobilization can be enhanced by priming, simultaneously or in sequence, one or more of a combination of different chemical compounds, cytokines, hormones, growth factors, etc. The interaction of chemokines and chemokine receptors enable tumor cells attachment or in close proximity to antigen presenting cells and immune cells which possess similar receptors in a micro niche environment. Severing the chemokine/chemokine receptor linkage by a cell adhesion inhibitor will release these specifically primed cell mixtures into the peripheral blood. The collection of these cells from the peripheral blood has never been described and is the basis of this invention.

Abstract: The present invention provides a non-liquid biomaterial that may be used as a surgical sealant, a suture support, a blood flow controller, an adhesion reducing agent, an adhesion preventing agent, a tissue support, a tissue filler, a wound dressing or a combination thereof. The non-liquid biomaterial may comprise a blood derived material such as plasma, platelet poor plasma, platelet rich plasma or a material derived from blood containing tissue aspirate, such as bone marrow aspirate, a protein binding agent and a polymerizing agent. Methods for making and using the non-liquid biomaterial are also provided.

Abstract: This invention is directed to therapeutic compositions containing non-MHC-restricted Tcells/NK-cells in combination with MHC-restricted T-cells and especially to therapeutic compositions, which comprise LAK cells. Furthermore, the present invention is directed to the use of the above combination in the treatment of tumors in humans, which tumors show a missing, low or aberrant expression of MHC class Ia or Ib molecules. By using the aforementioned compositions/combinations it is possible to provide a balanced selective pressure against emergence of tumor cell variants that would otherwise escape immune detection.

Abstract: A method of treating a human subject with cancer is disclosed. A pharmaceutical composition is administered to the subject, the pharmaceutical composition comprising human leukocytes and a replication-competent oncolytic virus in suspension in a physiologically acceptable solution. Alternatively the pharmaceutical composition comprises human leukocytes or platelets infected with an oncolytic virus.

Abstract: The present invention provides a method of treating Th2-associated diseases and disorders by modulating the expression or secretion of IL-4, IL-5 and IL-13 using interferon lambda (IFN-?). For Th2-associated diseases and disorders, cells of a patient having a Th2-associated disease or disorder are treated ex vivo, with IFN-? and returned to the patient.

Abstract: Disclosed are therapeutic, blood-derived activated leukocyte compositions, methods of making them, and methods of using the compositions to repair or promote the prevention and healing of wounds.

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