Abstract: Fibrosis arises as part of a wound healing response that maintains organ integrity following catastrophic tissue damage, but can also contribute to a variety of human pathologies, including liver cirrhosis. The invention demonstrates that cellular senescence acts to limit the fibrogenic response to tissue damage, thereby establishing a role for the senescence program in pathophysiological settings beyond cancer. Accordingly, the methods of the invention relate to modulating cellular senescence in disease tissue that have elevated numbers of senescent cells, such as in fibrotic tissues.

Abstract: Provided are natural and synthetic immunomodulatory polymeric antigens (SPAs), compositions containing SPAs, and methods of using these natural and synthetic SPAs and compositions to prevent or treat inflammatory pathologies.

Abstract: A method of determining responsiveness to cancer treatment is disclosed. The method comprises analyzing a frequency of tumor infiltrating lymphocytes (TILs) having a CD8+CD28?CD152? signature in a sample of the subject, wherein a frequency of TILs having the CD8+CD28?CD152? signature above a predetermined level is indicative of a positive responsiveness to cancer treatment. Other signatures reflecting responsiveness to cancer treatment are also disclosed. In addition, methods of treating cancer based on these signatures are also disclosed.

Abstract: Methods for preparing ex vivo T cell cultures using IL-21 compositions for use in adoptive immunotherapy are described. Addition of IL-21 to cultures of non-terminally differentiated T cells population, either isolated or present in peripheral blood mononuclear cells are exposed to one or more tumor antigens, and in the presence of IL-21 compositions and antigen presenting cells (APCs), the resulting T cell population has an enhanced antigen-specificity, and can be reintroduced into the patient. Methods are also disclosed for identifying tumor antigens by culturing T cell populations exposed to IL-21 compositions and APCs in the presence of tumor material.

Abstract: The invention relates to the use of CD Id-independent NKT cells, for the preparation of a pharmaceutical composition for treating a tumor in a patient. Said CD1d-independent NKT cells may be obtained by (a) culturing a population of T cells under conditions which suppress TGF? signalling pathway, and (b) selecting the cells which exhibit at least one NK marker.

Abstract: The instant invention provides TCRs having one or more amino acid substitutions that bind to the AL9 epitope of the HIV protein vpr (AIIRILQQL (SEQ ID NO: 1)).

Abstract: Compositions comprising human Tr1 cells directed to a food antigen from common human diet and methods for treating an intestinal inflammatory condition.

Abstract: The present invention relates to scaffolds which can be used as medical devices for guided tissue regeneration and repair, in particular the invention is directed to a scaffold comprising fibres having a mean fibre diameter of between from about 1.2 to 4.0 microns, wherein the fibres comprise a glycolide. The invention further relates to the use of the scaffolds for the selective capture of cell populations for a cell source material.

Abstract: A phosphazene-based polymer hydrogel with a chemical cross-linkings formed by radiating ultraviolet (UV) and/or mixing with cross-linking agent and/or enzyme, a method of preparing the same, and a hydrogel forming a chemical cross-linking by radiating ultraviolet and/or mixing with a cross-linking agent and/or an enzyme; where the hydrigel shows a sol-gel behavior and has an excellent solidity by containing the phosphazene-based polymer that is capable of cross-linking at a certain concentration, are provided.

Abstract: The invention is directed to a modified T cell receptor (TCR) comprising an amino acid sequence of a wild-type (WT) TCR with one or more amino acid substitutions in the CDR2 and/or CDR3 regions of the alpha and/or beta chains of the TCR, wherein the modified TCR, as compared to the WT TCR, (i) has an enhanced ability to recognize target cells when expressed by CD4+ T cells and/or CD8+ T cells and (ii) does not exhibit a decrease in antigen specificity when expressed by the CD4+ T cells and/or CD8+ T cells. Polypeptides, proteins, nucleic acids, recombinant expression vectors, host cells, populations of cells, antibodies, and pharmaceutical compositions related to the modified TCR also are part of the invention. Further, the invention is directed to methods of treating or preventing a disease in a host and methods of detecting a diseased cell in a host.

Abstract: Methods and compositions for the treatment or prevention of diseases or disorders including media conditioned by mesenchymal stem cells and BCL2A1 are provided. Methods for the production of therapeutic or preventative compositions contacted with BCL2A1 are also provided.

Abstract: This invention relates to the in vivo expansion of NKT cells by their exposure to mature dendritic cells expressing ?-galactosyl ceramide and to methods of use thereof in modulating immune responses, such as anti-cancer responses, and enhancing memory responses.

Abstract: Compositions and methods for the delivery of a protein of interest are provided.

Abstract: The invention provides isolated regulatory T cells and methods of obtaining regulatory T cells. The invention also provides methods for inhibiting an antigen-specific immune response (e.g., graft rejection, an autoimmune disorder, graft versus host disease, a response to a tumor cell, a response to an infection, and a response to an allergen) in a subject requiring administering an isolated regulatory T cell to the subject. The invention further provides methods for treating or modulating an antigen-specific immune response in a subject requiring administering a regulatory T cell to the subject.

Abstract: The present invention relates to immunotherapeutic methods, and molecules 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 T-helper cell peptide epitopes, alone or in combination with other tumor-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumor immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumor cell lines which can be used in vaccine compositions for eliciting anti-tumor immune responses.

Abstract: The present invention relates to immunotherapeutic methods, and molecules and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumour-associated T-helper cell peptide epitopes, alone or in combination with other tumour-associated peptides, that serve as active pharmaceutical ingredients of vaccine compositions which stimulate anti-tumour immune responses. In particular, the present invention relates to 49 novel peptide sequences derived from HLA class II molecules of human tumour cell lines which can be used in vaccine compositions for eliciting anti-tumour immune responses.

Abstract: The present invention relates to a method for producing dendritic cells and their use in medicaments by genetic engineering aimed at functionally improving their therapeutic efficacy in the treatment of cancer, microbial infections, allergies, auto-immune diseases or organ and stem cell transplant rejection.

Abstract: Modular aAPCs and methods of their manufacture and use are provided. The modular aAPCs are constructed from polymeric microparticles. The aAPCs include encapsulated cytokines and coupling agents which modularly couple functional elements including T cell receptor activators, co-stimulatory molecules and adhesion molecules to the particle. The ability of these aAPCs to release cytokines in a controlled manner, coupled with their modular nature and ease of ligand attachment, results in an ideal, tunable APC capable of stimulating and expanding primary T cells.

Abstract: This invention provides compositions and methods for treating a subject suffering from a disease or disorder of the nervous system, associated with an inflammatory response. This invention further provides a pharmaceutical composition comprising, inter alia, an agent which increases brain levels of interferon-?; and an agent which reduces the number of brain T regulatory (Treg) cells, and optionally further comprising an agent which suppresses neurotoxic inflammatory brain responses.

Abstract: A method of generating a population of dendritic cell (DC) precursors includes obtaining a population of progenitor cells from a subject and culturing the progenitor cells in a culture medium. The culture medium can include Flt3 ligand and interleukin-6 and be free of granulocyte-macrophage colony-stimulating factor.

Abstract: Disclosed is a method for regulation of airway hyperresponsiveness by modulating the action of ?? T cells in a patient. Also disclosed are methods for identifying compounds that regulate airway hyperresponsiveness by modulating ?? T cell action.

Abstract: The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.

Abstract: The present invention relates to systems and devices to treat and/or prevent inflammatory conditions within a subject and to related methods. More particularly, the invention relates to systems, devices, and related methods that sequester leukocytes and/or platelets and then inhibit their inflammatory action.

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: This invention is directed to the targeting of proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule and methods of use thereof. Nucleic acids, vectors comprising the same, and compositions for targeting proteins or peptides of interest to an autophagosome, for their presentation on a major histocompatibility complex (MHC) class II molecule are disclosed as are methods of use thereof for stimulating or enhancing immune responses in a subject.

Abstract: A method for stimulating prosaposin receptor activity in a cell by transfecting the cell with a DNA or RNA molecule encoding prosaposin or a prosaposin receptor agonist. The DNA or RNA molecule is administered either in vivo or used to transfect neural cells or neural stem cells ex vivo followed by reintroduction of the cells into an individual.

Abstract: The present invention provides methods and compositions for expanding T regulatory cells ex vivo or in vivo using one or more SAP agonists. The methods and compositions are useful in the treatment of autoimmune diseases and in preventing foreign graft rejection.

Abstract: A micro-scale artificial gland is disclosed in the form of an independent unit for promoting biological activity. The artificial gland includes cells formed in a membrane enclosing a reservoir. The reservoir is a bio-reactor capable of containing a product of activity of the cells. The reservoir comprises a gas, a liquid, and a gel and preferably also contains nanoparticles, a buffer, a surfactant, and, a gel precursor. The reservoir may also contain cells. Nanoparticles may also surround the artificial gland to form a protective coating. A variety of methods are disclosed for making the artificial gland by directed assembly of cells into the artificial micro-gland by gel, liquid or bubble templating. All involve coating the surface of gel, droplet or bubble with the living cells and the stabilizing the cells on the surface of gels, droplets or bubbles.

Abstract: A method for the generation of antigen-specific T-cell preparations for adoptive therapy is provided, comprising the steps of obtaining lymphoid cells from the bone marrow of a patient in a first step, expanding the lymphoid cells in cell culture medium ex-vivo in the presence of at least one of IL2 and IL7 and or more antigens, yielding a T-cell preparation, and isolating the T-cell preparation from the culture medium in an isolation step. T-cell preparations provided according to the inventive method, and the use of such T-cell preparations for the treatment of infectious disease and cancer is also provided.

Abstract: The present invention relates to a method for treatment of cancer, which comprises the following steps (A) and (B): (A) applying a treatment which induces the reduction in lymphocytes to a patient; and (B), subsequent to step (A), administering lymphocytes to the patient promptly. The present invention also relates to a cancer therapeutic agent and a cancer treatment kit for use in the method. When the method is used as an immunoreconstructive therapy, the decrease in immunologic competence which may be caused by the reduction in lymphocytes can be avoided and, therefore, the risk of the occurrence of an infectious disease can be decreased.

Abstract: The present invention is directed to methods and compositions for slowing or inhibiting the growth of tumors and decreasing the size of existing tumors. The compositions include dendritic cells contacted with tumor/B-cell hybrid cells and various T-cells contacted with tumor/B-cell hybrid cells (TBH cells). The present invention further encompasses methods of generating such compositions and methods of use of such compositions.

Abstract: The present invention relates to improved autologous T cell vaccines and improved methods for their production. The invention is also directed to methods for treating autoimmune diseases such as multiple sclerosis or rheumatoid arthritis using autologous T cell vaccines. The invention further directed to the diagnosis of T associated diseases.

Abstract: The present invention is directed to a synthetic peptide comprising a sequence of amino acids containing at least a segment that is an analogue of a native peptide that specifically binds to HLA A0201 or HLA A0301 molecules on a cell characteristic of a pathophysiologic state in a mammal. The synthetic peptide may be derived form native peptides comprising a breakpoint region of the WT1 protein.

Abstract: The invention relates to the use of allogenic T lymphocytes for the preparation of a composition intended to be injected into a recipient patient as a conditioning for a transplantation of haematopoietic stem cells, said allogenic T lymphocytes expressing a molecule allowing their specific destruction.

Abstract: The present application relates to nucleic acids that encode a RNA switch responsive to a ligand that can control the expression of a gene product that affects the cell fate determination of a mammalian cell are provided. In some embodiments, the system can be used to control the proliferation or activation of mammalian cells in response to a ligand that can be provided exogenously to the mammalian cell or can be produced by the mammalian cell. The system can be used to promote the growth or proliferation of human T cells in response to an exogenous ligand applied to the cells. In one embodiment, the system detects the ligand through a RNA aptamer that modulates expression of a gene product through activation or inactivation of a ribozyme that modulates expression of the gene product.

Abstract: Compositions comprising Tr1 cells directed to a multiple sclerosis associated antigen and methods for treating multiple sclerosis.

Abstract: The invention is generally related to methods of treating autoimmune diseases, including both antibody-mediated and cell-mediated disorders.

Abstract: This disclosure relates to novel N-phenyl-2-pyrimidineamines and pharmaceutically acceptable salts thereof. This disclosure also provides compositions comprising a compound of this disclosure and the use of such compositions in methods of treating diseases and conditions that are beneficially treated by administering protein-tyrosine kinase inhibitors.

Abstract: A method for eliciting an immune response to an antigen in a subject via (a) loading isolated antigen presenting cells with an antigen ex vivo; and (b) administering the antigen presenting cells to a subject at a pre-treated site.

Abstract: The invention provides a method for preparing cell populations with anti-tumor immune response activity, which includes co-culturing tumor and mononuclear cell in a three-dimensional cell culture device, separating and amplifying the cell populations with anti-tumor immune response activity from the cultures. The present invention, at the same time, discloses the cell populations with anti-tumor immune response activity obtained by the method and the kit comprising the cell populations.

Abstract: With the current invention, we provide new methods of enhancing the T-cell stimulatory capacity of human dendritic cells (DCs) and their use in cancer vaccination. The method comprises the introduction of different molecular adjuvants to human DCs through transfection with at least two mRNA or DNA molecules encoding markers selected from the group of: CD40L, CD70, constitutively active TLR4 (caTLR4), IL-12p70, EL-selectin, CCR7 and/or 4-1 BBL; or in combination with inhibition of SOCS, A20, PD-L1 and/or STAT3 expression, for example through siRNA transfection. We could show a clear increase in the immunostimulatory capacity of DCs obtained in this way, enabling them to elicit an unexpectedly high T-cell immune response in vitro.

Abstract: The invention relates to the treatment of a tumor in a patient, by injecting T lymphocytes depleted of regulatory T lymphocytes, and expressing a molecule allowing their specific destruction, the patient receiving beforehand a non-myeloablative or myeloablative lymphopenic treatment.

Abstract: The invention provides methods of repairing damage to, or defects in, mammalian tissues or organs. In these methods, a particulate or non-particulate acellular matrix made from a tissue or organ other than the tissue or organ being repaired is placed in or on the organ or tissue that is being repaired.

Abstract: The invention provides a peptide comprising an agonist of a MHC Class I binding native sequence having amino acid substitution(s) and enhanced immunogenicity compared to the native sequence. The invention also provides methods comprising the administration of the peptide.

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: 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: An objective of the present invention is to provide safe viral vectors for gene therapy that can be introduced by a simple technique and sufficiently express genes of interest in vivo. The present inventors demonstrated that anti-tumor effect can be produced when a heparin-binding cytokine such as granulocyte macrophage colony stimulating factor (GM-CSF) and a chemokine such as TARC or RANTES are expressed in vivo using a viral vector based on a negative-strand RNA virus. The present inventors also demonstrated that the protective effect of the vector is superior to that of conventional adenovirus vectors. Thus, the present invention relates to negative-strand RNA viral vectors comprising a cytokine gene and a chemokine gene. The viral vectors are suitable for treatment of cancers, in particular, metastatic cancers. The present invention also provides compositions comprising such viral vectors, and gene therapy methods using them.

Abstract: The present invention relates to a pharmaceutical composition for inducing an immune response in a human or animal, comprising dendritic cells loaded with at least five cancer/testis antigen and no lineage specific differentiation antigens or substantially no lineage specific differentiation antigens provided from at least one cancer cell line, as well as to isolated cell lines expressing a multiplicity of cancer testis antigens and no differentiation antigens, and to a method of inducing an immune response in a human or animal using the composition of the invention.

Abstract: Provided are compositions and methods for enhancing immune responses to an antigen. The compositions contain an isolated population of CD8+T cells and an inhibitor of mammalian target of rapamycin (mTOR). The method for obtaining an enhanced immune response to an antigen in an individual entails administering to the individual the antigen and an inhibitor of mammalian target of rapamycin (mTOR). CD8+T cells may also be used for adoptive cell transfer (ACT) therapy.

Abstract: The present invention relates to antigen-Ig Ab fusion molecules and methods of using same, wherein antigen-Ig Ab fusion molecules include an antigen fused to an immunoglobulin molecule, fragment or variant thereof and wherein the fusing of the immunoglobulin molecule to the antigen does not alter the specificity or tertiary structure of important epitopes of the antigen. This method allows the direct quantification and isolation of antigen-specific B cells by flow cytometry in essentially any species.