Abstract: Methods and compositions for modifying T-cells in which PD1 and/or CTLA-4 is repressed and/or inactivated using fusion proteins such as artificial transcription factors and nucleases.

Abstract: The invention provides compositions and methods for treating ovarian cancer. Specifically, the invention relates to administering a genetically modified T cell having alpha-folate receptor (FR-alpha) binding domain and CD27 costimulatory domain to treat ovarian cancer. In an embodiment, the FR-alpha binding domain is fully human, thereby preventing a host immune response.

Abstract: Provided are methods, compounds, and compositions for reducing expression of ApoCIII mRNA and protein for treating, preventing, delaying, or ameliorating Fredrickson Type I dyslipidemia/FCS/LPLD, in a patient. Such methods, compounds, and compositions increase HDL levels and/or improving the ratio of TG to HDL and reducing plasma lipids and plasma glucose in the patient, and are useful to treat, prevent, delay, or ameliorate any one or more of pancreatitis, cardiovascular disease, metabolic disorder, and associated symptoms.

Abstract: Embodiments described herein relate to methods, devices, and computer systems thereof for the derivation of T CAR libraries (Universal Subject or Individual Subject) for personalized treatment of disease in a subject. In certain embodiments, differential screening of normal and diseased tissue expression data is utilized to determine disease-specific antigens and thereby generate T CAR cells reactive to such antigens to form a disease-specific library. In certain embodiments, determination of the most effective T CAR clones from the disease-specific library is based on the subject's own disease-specific antigens. In certain embodiments, a subject is treated with a therapeutically effective amount of T CAR clones.

Abstract: Cell based therapy comprises administration to the lung by injection into the blood system of viable, mammalian cells effective for alleviating or inhibiting pulmonary disorders. The cells may express a therapeutic transgene or the cells may be therapeutic in their own right by inducing regenerative effects.

Abstract: The present invention relates to methods of inducing or enhancing an immune response against an immunogen in a subject. The invention further includes isolated nucleic acid vaccines, cellular vaccines, fusion proteins, expression vectors, vaccines, and immunogenic compositions for use therein.

Abstract: Provided herein are compositions which exhibit novel diagnostic capabilities and allow to rapidly add functionality to adoptive immunotherapy. The compositions include isolated nucleic acids encoding proteins including antibody regions capable of binding compounds including a peptidyl moiety (e.g., a meditope). The recombinant proteins provided herein are useful, inter alia, for a broad variety of therapeutic and diagnostic purposes. For example, the recombinant proteins provided herein including embodiments thereof may be used as non-invasive means to characterize chimeric antigen receptor (CAR) T cells before and/or during treatment of diseases (e.g., cancer).

Abstract: The invention generally regards methods for providing hematopoietic cells and precursors of hematopoietic cells from a variety of cell sources, such as pluripotent stem cells or somatic cells. Also provided are therapeutic compositions including the provided hematopoietic cells and precursors of hematopoietic cells, and methods of using such for the treatment of subjects.

Abstract: Disclosed herein are methods and compositions for inhibiting viral entry into cells.

Abstract: The present invention relates in part to methods for producing tissue-specific cells from patient samples, and to tissue-specific cells produced using these methods. Methods for reprogramming cells using RNA are disclosed. Therapeutics comprising cells produced using these methods are also disclosed.

Abstract: The disclosure provides reagents, methods, and kits, for treating melanoma. The reagent encompasses interferon-gamma (IFN-gamma) responsive melanoma cells, where the cells are autophagic and non-apoptotic melanoma cells, and where the cells express MHC Class II. In another aspect, the reagent encompassed dendritic cells loaded with the IFN-gamma responsive, non-apoptotic, MHC Class II-expressing melanoma cells.

Abstract: The disclosure relates to the development of methods for making hematopoietic stem cells from differentiated cells by introducing and expressing transcription factors. More particularly, the disclosure provides methods for redirecting differentiated cells to a hematopoietic stem cell state or to a hemogenic endothelial cell state by direct programming with specific combinations of transcription factors.

Abstract: The present invention relates generally to systems and methods for preparing, storing, shipping and using skin equivalents made by organotypic culture. In particular, the present invention relates to systems and methods for producing, transporting, storing and using skin equivalents produced by organotypic culture at reduced temperatures, preferably from 2-8 degrees Celsius to ambient temperature. The methods include sterile packaging of the grafts so that the sterility and integrity of the package is maintained until the time of use for grafting purposes.

Abstract: The present invention relates to a method of non-invasively monitoring the expression of a gene of interest in a cell when contacting said cell with a compound influencing the expression of said gene of interest. The present invention is also concerned with different isolated nucleic acid molecules comprising a coding sequence. Said coding sequence comprises a gene of interest-sequence encoding a gene of interest-polypeptide fused to a reporter sequence encoding a fluorescent reporter polypeptide and is operatively coupled to a promoter sequence. The present invention is also concerned with the use of a method and a nucleic acid molecule of the invention for delivering a compound influencing the expression of a gene of interest in a cell, monitoring the delivery of said compound as well as monitoring the influence on the expression of said gene of interest induced by said compound at the same time.

Abstract: The present invention relates to a method of identifying and separating non-regulatory T-cells (conventional T-cells) from a mixture comprising regulatory T-cells by using of the CD154 molecule (CD40 ligand) through depletion of CD154+ T-cells from the mixture or in combination with additional positive selection of Treg using markers that are specific for regulatory T-cells, such as for example, CD25, GITR, CTLA4 or markers which are specific for activated regulatory T-cells, such as, for example, CD137, “latent TGF-beta (LAP)”, GARP (LRRC32), CD121a/b, thereby generating a cell composition of activated Treg cells. The invention relates also to a kit comprising an antibody for detecting CD154 and at least one additional antibody for detecting markers for activated or non-activated regulatory T-cells. The antibodies can be coupled to a fluorescent dye or magnetic microparticles.

Abstract: The invention provides a chimeric receptor comprising NKG2D, DAP10 and CD3 zeta. Also disclosed is a composition comprising this chimeric receptor and methods for making and using it to enhance the cytotoxicity and antitumor capacity of NK cells. The invention also encompasses methods for the use of NKG2D-DAP10-CD3 zeta polypeptides, vectors and cells in methods for treating cancer and other proliferative disorders, as well as infectious diseases.

Abstract: A method of transforming human cells into mechanosensory hair cells (MHCs), such as inner hear hair cells in the cochlea and vestibular organs, can include: causing human Wharton's jelly cells (hWJCs) to increase expression of or biological function of HATH1 so as to transform the hWJCs into MHCs. The method can include; administering a nucleic acid that encodes HATH1 to the hWJCs; causing inhibited expression of or biological function of HES1 and/or HES5 in the hWJCs; administering a nucleic acid that inhibits HES1 and/or a nucleic acid that inhibits HES5 to the hWJCs; causing inhibited expression of or biological function of HES1 and/or HES5 in the WJCs by administering a nucleic acid that inhibits HES1 and/or a nucleic acid that inhibits HES5; nucleic acids are administered includes a sequence of SEQ ID NO: 2, SEQ ID NO: 3, and/or SEQ ID NO: 4.

Abstract: Methods and compositions for improving immune system function are provided. These methods find particular use in improving immune system function in individuals with a condition in which naïve lymphocytes comprise elevated amounts of DNA double strand breaks (DSB), for example, individuals with Rheumatoid Arthritis, individuals that have received a bone marrow transplant, or elderly individuals, e.g. individuals that are 50 or more years old. Also provided are methods and compositions for screening for novel compounds that will improve immune system function in such individuals.

Abstract: The invention relates to an isolated multipotent glomerular mesenchymal stem cell derived from adult human kidney (hGL-MSC), which is characterized by the marker profile CD133?, CD146+, CD34? and CD105+. A method of preparing the hGL-MSC of the invention form decapsulated glomeruli is also disclosed, as well as the uses of the hGL-MSC of the invention in the regenerative treatment of the kidney, particularly for the treatment of injuries or diseases affecting renal glomeruli.

Abstract: The present invention provides methods for producing cell populations enriched for stable, regulatory T cells (Tregs). In particular, the invention relates to methods for culturing T cells such that the final culture is enriched for stable, regulatory T cells. It also relates to methods for stabilizing regulatory T cells. Also provided are compositions enriched for stable, regulatory T cells, which are useful for treating individuals in need of such treatment. The methods and compositions disclosed herein can also be used to treat an individual suffering from an immune-mediated disease.

Abstract: The present invention relates to novel compositions and methods to induce, and/of modulate bio-electrical rhythms (e.g. in cardiac, neuronal and pancreatic cells) by fine-tuning the activity of HCN-encoded pacemaker channels via a novel protein- and genetic-engineering approach to augment or attenuate the associated physiological responses (e.g. heart beat, neuronal firing, insulin secretion, etc) for achieving various therapeutic purposes (e.g. sick sinus syndrome, epilepsy, neuropathic pain, diabetes, etc).

Abstract: Methods and systems for releasing growth factors are disclosed. In certain embodiments, a blood sample is exposed to a sequence of one or more electric pulses to trigger release of a growth factor in the sample. In certain embodiments, the growth factor release is not accompanied by clotting within the blood sample.

Abstract: The invention provides compositions and methods for the preparation of biocompatible biomaterials from adipose tissue. Biocompatible biomaterials are cellular or acellular biomaterials. The invention further provides methods of use of the biocompatible biomaterials.

Abstract: The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA that target apolipoprotein C-III (APOC3) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for the treatment of lipid diseases or disorders such as atherosclerosis or a dyslipidemia such as hypertriglyceridemia or hypercholesterolemia).

Abstract: Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

Abstract: Macroporous 3-D tissue engineering scaffold are manufactured by contacting an article comprising multiple distinct macroparticulate porogens distributed within a polymer scaffold, wherein the porogens are selectively and sequentially dissolvable by corresponding biocompatible stimuli.

Abstract: The present invention uses neural stem cells in the manufacture of a medicament for the treatment of a patient suffering peripheral arterial disease. The invention is particularly suited for treating limb ischemia or Buerger's disease.

Abstract: The present invention encompasses methods and compositions for reducing an immune response to a transplant in a recipient by treating said recipient with an amount of liver stromal cells effective to reduce or inhibit host rejection of the transplant. Also disclosed is a method of inducing a reduced immune response against a host by foreign tissue, i.e., graft versus host disease, by treatment with liver stromal cells.

Abstract: Brown adipose tissue (“BAT”) progenitor cells and methods for identifying BAT progenitor cells in a population of cells are provided. Methods are also provided for inducing differentiation of BAT progenitor cells into differentiated brown adipocytes, inducing expression or increased activity levels of BAT uncoupling protein-1 (“UCP1”), and for identifying agents capable of inducing differentiation of BAT progenitor cells into brown adipocytes and/or inducing expression or increased activity levels of UCP1. Differentiated brown adipocytes and agents and methods for inducing differentiation of BAT progenitor cells can be used for treatment of or the making of medicaments for the treatment of metabolic diseases or conditions in a patient such as obesity, overweight, impaired glucose tolerance, insulin-resistance, type 2 diabetes, dyslipidemia, hypertension, cardiovascular diseases, metabolic syndrome, and the like.

Abstract: A resorbable bone graft scaffold material, including a plurality of overlapping and interlocking fibers defining a scaffold structure, plurality of pores distributed throughout the scaffold, and a plurality of glass microspheres distributed throughout the pores. The fibers are characterized by fiber diameters ranging from about 5 nanometers to about 100 micrometers, and the fibers are a bioactive, resorbable material. The fibers generally contribute about 20 to about 40 weight percent of the scaffold material, with the microspheres contributing the balance.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain without affecting glycemic control. In particular, the invention provides novel glucagon analog peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the glucagon-like peptide-1 (GLP-1) receptor as compared to human glucagon.

Abstract: The disclosure relates to a method of reprogramming one or more somatic cells, e.g., partially differentiated or fully/terminally differentiated somatic cells, to a less differentiated state, e.g., a pluripotent or multipotent state. In further embodiments the invention also relates to reprogrammed somatic cells produced by methods of the invention, to uses of said cells, and to methods for identifying agents useful for reprogramming somatic cells.

Abstract: The present invention relates to the use of a DNA expression construct comprising a dumbbell-shaped circular strand of deoxyribonucleic acids and provides such a construct with a double-stranded stem and single-stranded loops located at both ends of the stem, wherein the stem comprises complementary deoxyribonucleic acids of the circular strand with a promotor sequence, a coding sequence and a termination signal to be administered by jet injection for the treatment of cancer.

Abstract: The invention provides compositions and methods for selectively reducing the expression of a gene product from a desired target gene, as well as treating diseases caused by expression of the gene. The method involves introducing into the environment of a cell an amount of a double-stranded RNA (dsRNA) such that a sufficient portion of the dsRNA can enter the cytoplasm of the cell to cause a reduction in the expression of the target gene. The dsRNA has a first oligonucleotide sequence that is between 26 and about 30 nucleotides in length and a second oligonucleotide sequence that anneals to the first sequence under biological conditions. In addition, a region of one of the sequences of the dsRNA having a sequence length of from about 19 to about 23 nucleotides is complementary to a nucleotide sequence of the RNA produced from the target gene.

Abstract: Disclosed are methods for manipulating and expanding stem cell populations, including adult stem cells, the cells produced by such methods, and various protein constructs related thereto.

Abstract: A reprogramming gene-loaded Sendai viral vector comprising Sendai virus genes and reprogramming genes, wherein the Sendai virus genes include an NP gene, P/C gene, M gene, F gene, HN gene and L gene, wherein each of the M gene, the F gene and the FIN gene is from a Sendai virus strain Cl.151-derived gene and wherein at least one of the M gene, the F gene and the HN gene is functionally deleted and the L gene encodes the amino-acid sequence of the L protein in which the amino-acid residue at position 1618 is valine and a method of producing the same.

Abstract: The present invention concerns products containing (i) at least one nucleic acid sequence coding for the human somatostatin 2 receptor protein (sst2) having the sequence SEQ ID NO: 1, ortholog or derivative thereof, (ii) at least one nucleic acid sequence coding for the human deoxycytidine kinase protein (dck) having the sequence SEQ ID NO:2, ortholog or derivative thereof, (iii) at least one nucleic acid sequence coding for the human uridine monophosphate kinase protein (umk) having the sequence SEQ ID NO: 3 ortholog or derivative thereof, and (iv) gemcitabine, as a combined preparation for simultaneous, separate, or sequential use for treating cancer in a subject.

Abstract: The invention is directed to a method for isolating stromal cells to form a therapeutic composition; and administering said therapeutic composition to the subject. A further embodiment of the invention is directed to therapeutic compositions comprising isolated stromal cells.

Abstract: The present invention relates to a transgenic pig that expresses sTNFR1-Fc, wherein a gene encoding sTNFR1-Fc, which is a fusion protein of the extracellular domain of human soluble tumor necrosis factor receptor (sTNFR1) and an immunoglobulin Fc region, is introduced; a method for preparing the same; an organ isolated from the transgenic pig; a somatic donor cell line inserted with sTNFR1-Fc gene; a method for preparing a blood sample comprising sTNFR1-Fc; and a method for preparing human sTNFR1-Fc from the blood sample of the transgenic pig. As the transgenic pig can suppress immune response and inflammatory response by secreting an inhibitory substance that suppresses the activity of TNF-? in blood, it can be effectively used for xenograft. Furthermore, since the transgenic pig has a blood type O, it can be transplanted for suppressing inflammatory response, regardless of a blood type of recipient.

Abstract: The methods of the present application describe that introduction of physiologically relevant miRNAs can enhance or modulate somatic cell reprogramming, generating induced pluripotent stem cells (iPS cells). These miRNAs did not further enhance reprogramming in the presence of cMyc. Furthermore, unlike previously described methods of generating iPS cells, such as through the introduction of genetic elements using viruses, the methods of the present invention reduce the risk of activating oncogenes in the iPS cells. The methods of the invention generate iPS cells that can be free of genetic modifications and thus have greater potential for use as therapeutic agents than those generated by existing methods.

Abstract: The present invention relates to mesenchymal stem cells (MSC) genetically modified to express sST2 or parts thereof for use in the treatment of airway immune inflammatory and lung diseases, wherein said mesenchymal stem cells are not human embryonic stem cells. The present invention also relates to pharmaceutical compositions comprising said mesenchymal stem cells.

Abstract: The present invention provides a composition for delivering a protein vaccination candidate to a mammalian subject having a Leishmania transfected for expressing a cDNA sequence for encoding the protein vaccination candidate, and the Leishmania containing a photosensitizer.

Abstract: The disclosure herein relates generally to immunotherapy and, more specifically, to the use of immunotherapy for treating tumors and pathogen infected tissues. The immunotherapy relates to first priming patients with allogeneic cells designed to be rejected by a Th1 mediated mechanism, then inducing in situ necrosis or apoptosis in a tumor or pathogen infected lesion. Necrosis or apoptosis can be induced by methods such as cryotherapy, irreversible electroporation, chemotherapy, radiation therapy, ultrasound therapy, ethanol chemoablation, microwave thermal ablation, radiofrequency energy or a combination thereof applied against at least a portion of the tumor or pathogen infected tissue. One or more doses of allogeneic cells (e.g., Th1 cells) are then delivered within or proximate to the tumor or pathogen-infected tissue in the primed patient. The present invention provides an immunotherapeutic strategy to develop de-novo systemic (adaptive) immunity to a tumor or pathogen.

Abstract: Provided are methods for activating an antigen-presenting cell and eliciting an immune response by inducing an inducible pattern recognition receptor adapter, or adapter fragment, and CD40 activity. Also provided are nucleic acid compositions comprising sequences coding for chimeric proteins that include an inducible CD40 peptide and an inducible pattern recognition receptor adapter or adapter fragment.

Abstract: We formulated multiple TLR agonists into GVAX (lethally irradiated tumor cell vaccines engineered to secrete GM-CSF). Specifically, GLA and R848, TLR4 and TLR7/8 agonists found to be safe in patients, were formulated with GVAX (TEGVAX—for TLR agonists enhanced GVAX), and this formulation was effective in producing anti-tumor responses in 3 different preclinical models, including palpable B16. These anti-tumor responses were correlated with increased CD4 and CD8 T-cells that can secrete IFN? circulating in the tumor microenvironment as well as significantly higher level of p15E specific CTL mediated cell killing in mice treated with TEGVAX in comparison to controls. When combined with anti-PD-1 antibody, TEGVAX was able to induce regression of established B16 tumors.

Abstract: A method of treating a BORG expressing cancer includes administering a therapeutically effective amount of at least one BORG inhibiting agent to the BORG overexpressing cancer cells of the subject.

Abstract: A use of a stem cell conditioned medium to inhibit melanin formation for skin whitening is revealed. First, mesenchymal stem cells are cultured in a cell culture dish containing complete growth media. After mesenchymal stem cells are sub-cultured in a complete growth media for three times, a conditioned medium can be acquired from the basal media.

Abstract: A use of a stem cell conditioned medium to inhibit oxidation for anti-aging skin. First, mesenchymal stem cells are cultured in a cell culture dish containing a complete growth medium. After mesenchymal stem cells are sub-cultured in the complete growth media for three times and transferred to a basal medium, a conditioned medium can be acquired from the basal medium.

Abstract: A use of a stem cell conditioned medium to induce ZO-1 proteins expression for skin regeneration, repair and finning is revealed herein. First, mesenchymal stem cells are cultured in a cell culture dish containing complete growth media, wherein the complete growth media include ?-MEM, fetal bovine serum, and human-basic fibroblast growth factors. After mesenchymal stem cells are sub-cultured in the complete growth media for three times, a conditioned medium which can effectively increase the activation of tight junction protein Zonula occludens-1 (ZO-1) can be acquired from the basal medium.

Abstract: The present invention relates to B7-H4-specific compositions and methods of use thereof.