Abstract: Disclosed herein are extracellular vesicles comprising an immunomodulating component. Also provided are methods for producing the extracellular vesicles and methods for using the extracellular vesicles for treating cancer, GvHD, and autoimmune diseases.

Abstract: The invention provides compositions and methods for generating improved T cells having increased Ezh2 activity and methods of use thereof in the treatment of cancer and chronic infection.

Abstract: Described herein are immunomodulatory fusion proteins containing an extracellular binding domain and an intracellular signaling domain, wherein binding of a target can generate a modulatory signal in a host cell, such as a T cell. Some immunomodulatory fusion proteins as described comprise a SIRP? extracellular component and hydrophobic and intracellular components comprising transmembrane and/or signaling domains of a CD28, respectively. Such fusion proteins are capable of delivering a positive or costimulatory signal in response to a binding event that in a natural setting would result in an inhibitory signal. Uses of immune cells expressing such immunomodulatory fusion proteins to treat certain diseases, such as cancer or infectious disease, are also described.

Abstract: Compounds for use in the prevention and/or treatment of immunological diseases, particularly rheumatoid arthritis, systemic lupus erythematosus and lupus nephritis, are described, characterized by the subcutaneous administration of isoforms of C4BP lacking the beta chain or polypeptides comprising the CCP6 region of the alpha chain of C4BP no more than once a week or at a dose ranging from 0.24 mg/m2 to 9.99 mg/m2. Pharmaceutical compositions comprising from 0.45 mg to 18.90 mg of these compounds for the prevention and/or treatment of these diseases are also described.

Abstract: The present invention relates to gene and cell therapy using a cell fusion technology and more particularly, cells overexpressing hemagglutinin neuraminidase (HN) and fusion (F) proteins have effects of enhancing cell fusion with other cells, restoring cell damage through the cell fusion with damaged cells, and transferring a normal gene. Therefore, when a vector including genes encoding the HN and F proteins of the present invention or a cell transformed with the vector is clinically applied to neurodegenerative diseases, muscular diseases, and the like, an effect of reducing the damage of damaged cells through cell fusion can be expected.

Abstract: The present disclosure provides modified immune cells (e.g., modified T cells) comprising a chimeric antigen receptor (CAR) having affinity for a prostate-specific membrane antigen (PSMA) (e.g., human PSMA). The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor. The present disclosure provides modified immune cells (e.g., modified T cells) comprising a CAR having affinity for PSMA and a dominant negative receptor and/or a switch receptor, wherein the modified cell is capable of expressing and secreting a bispecific antibody.

Abstract: The invention relates to the treatment of various injuries, disorders, dysfunctions, diseases, and the like with MAPCs, without the need for adjunctive immunosuppressive treatment.

Abstract: Disclosed are methods, compositions of matter, and kits useful for augmentation of cells through modification of cellular membrane properties following ex vivo treatment.

Abstract: Disclosed herein are RNA polynucleotides comprising a 5? Cap, a 5? UTR comprising a cap proximal sequence disclosed herein, and a sequence encoding a payload. Also disclosed herein are compositions and medical preparations comprising the same, and methods of making and using the same.

Abstract: Provided are binding molecules, such as TCRs or antigen binding fragments thereof and antibodies and antigen-binding fragments thereof, such as those that recognize or bind human papilloma virus (HPV) 16, including HPV 16 E6 and HPV 16 E7. Also provided are engineered cells containing such binding molecules, compositions containing the binding molecules or engineered cells, and methods of treatment, such as administration of the binding molecules, engineered cells, or compositions.

Abstract: The present invention relates to peptides, proteins, 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 T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Abstract: The present invention relates to T cell compositions and methods of using the same in the context of therapy and treatment. In particular, the invention provides chimeric antigen receptor (CAR) T cells that are modified to maintain functionality under conditions in which unmodified CAR T cells display exhaustion. Compositions and methods disclosed herein find use in inhibiting or reversing CAR T cell exhaustion (e.g., by modulating CAR surface expression) thereby enhancing CAR T cell function. Compositions and methods of the invention fmd use in both clinical and research settings, for example, within the fields of biology, immunology, medicine, and oncology.

Abstract: The present invention relates to compositions and methods configured to deliver a stimulus (e.g., a therapeutic agent or a therapeutically beneficial signal) to a cell, tissue, organ, or organism. The stimulus is applied at least twice, and the first and second applications are separated by a rest period in which no further stimulus is actively applied. The rest period is of a duration (e.g., about 1-6 hours) sufficient to provoke an enhanced response to the second stimulus.

Abstract: Provided herein are compositions comprising modified caveolin-1 (Cav-1) peptides. Further provided are methods of using the modified Cav-1 peptides for the treatment of lung infections or acute or chronic lung injury, particularly lung fibrosis.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: The present invention relates to a bispecific polypeptide molecule comprising a first polypeptide chain and a second polypeptide chain providing a binding region derived from a T cell receptor (TCR) being specific for a major histocompatibility complex (MHC)-associated peptide epitope, and a binding region derived from an antibody capable of recruiting human immune effector cells by specifically binding to a surface antigen of said cells, as well as methods of making the bispecific polypeptide molecule, and uses thereof.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus, the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: Provided is an anti-mesothelin chimeric antigen receptor that specifically binds to mesothelin. The anti-mesothelin chimeric antigen receptor according to an aspect exhibits a specific binding ability for mesothelin, and thus, may be useful for preventing or treating cancer in which mesothelin is overexpressed.

Abstract: Provided are modified immune cells including tumor infiltrating lymphocyte (TIL) or B cells, a composition comprising the immune cells, and a method of treating neoplastic or cancer conditions comprising administering to a subject the immune cells.

Abstract: Provided herein are T-cell receptor (TCR) fusion proteins (TFPs) having specificity for one or more tumor cell associated antigens, T cells engineered to express one or more TFP, and methods of use thereof for the treatment of diseases, including cancer.

Abstract: A gene and cell therapy using a cell fusion technology is proposed. Cells overexpressing hemagglutinin neuraminidase (HN) and fusion (F) proteins have effects of enhancing cell fusion with other cells, restoring cell damage through the cell fusion with damaged cells, and transferring a normal gene. Therefore, when a vector including genes encoding the HN and F proteins of the present invention or a cell transformed with the vector is clinically applied to neurodegenerative diseases, muscular diseases, and the like, an effect of reducing the damage of damaged cells through cell fusion can be expected.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: The present application provides materials and methods for treating a patient with Alpha-1 antitrypsin deficiency (AATD) both ex vivo and in vivo. In addition, the present application provides materials and methods for editing the SERPINA1 gene in a cell by genome editing.

Abstract: The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a hematopoietic cell.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: The present invention includes compositions and methods for an HLA-A2 specific chimeric antigen receptor (CAR). In certain embodiments the HLA-A2 specific CAR is expressed on a T regulatory cell. In certain embodiments, the HLA-A2 specific CAR protects transplanted tissue from rejection.

Abstract: Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS.

Abstract: Nucleases and methods of using these nucleases for expressing an antibody from a safe harbor locus in a secretory tissue, and clones and animals derived therefrom.

Abstract: The invention relates to retroviral producer cell comprising nucleic acid sequences encoding: gag and pol proteins; envelope protein or a functional substitute thereof; amplifiable selection marker; and the RNA genome of the retroviral vector particle, wherein said nucleic acid sequences are all integrated at a single locus within the retroviral producer cell genome. The invention also relates to nucleic acid vectors comprising a non-mammalian origin of replication and the ability to hold at least 25 kilobases (kb) of DNA, characterized in that said nucleic acid vector comprises retroviral nucleic acid sequences encoding: gag and pol proteins, and an env protein or a functional substitute thereof. The nucleic acid vector additionally comprises nucleic acid sequences encoding an amplifiable selection marker. The invention also relates to uses and methods using said nucleic acid vector in order to produce stable retroviral packaging and producer cell lines.

Abstract: RNA encoding an immunogen is delivered to a large mammal at a dose of between 2 ?g and 100 ?g. Thus the invention provides a method of raising an immune response in a large mammal, comprising administering to the mammal a dose of between 2 ?g and 100 ?g of immunogen-encoding RNA. Similarly, RNA encoding an immunogen can be delivered to a large mammal at a dose of 3 ng/kg to 150 ng/kg. The delivered RNA can elicit an immune response in the large mammal.

Abstract: The present invention relates to a composition for inducing direct conversion from a somatic cell into one or more kinds selected from the group consisting of an induced Hepatic stem cell (iHSC), a hepatocyte, and a cholangiocyte, and a method of direct conversion of a somatic cell into one or more kinds selected from the group consisting of an induced Hepatic stem cell, a hepatocyte, and a cholangiocyte.

Abstract: The presently disclosed subject matter provides for expression cassettes that allow for expression of a globin gene or a functional portion thereof, vectors comprising thereof, and cells transduced with such expression cassettes and vectors. The presently disclosed subject matter further provides methods for treating a hemoglobinopathy in a subject comprising administering an effective amount of such transduced cells to the subject.

Abstract: An object of the present invention is to provide novel mesenchymal stem cells demonstrating superior therapeutic effects against various diseases, a novel pharmaceutical composition containing these mesenchymal stem cells, and a method for preparing the same. The present invention relates to ROR1-positive mesenchymal stem cells. The ROR1-positive mesenchymal stem cells are preferably positive for CD29, CD73, CD90, CD105 and CD166 and are derived from umbilical cord or adipose tissue.

Abstract: The present disclosure provides RNA-guided CRISPR-Cas effector proteins, nucleic acids encoding same, and compositions comprising same. The present disclosure provides ribonucleoprotein complexes comprising: an RNA-guided CRISPR-Cas effector protein of the present disclosure; and a guide RNA. The present disclosure provides methods of modifying a target nucleic acid, using an RNA-guided CRISPR-Cas effector protein of the present disclosure and a guide RNA. The present disclosure provides methods of modulating transcription of a target nucleic acid.

Abstract: The present invention relates to an exosome for stimulating T cells and the pharmaceutical use thereof. Immune exosomes secreted from artificial antigen-presenting cells which express HLA, CD32, and co-stimulatory molecules CD32, CD80, CD83, and 4-1BBL are used to stimulate naive CD8+ T cells whereby preventive and therapeutic effects on tumors, pathogen infections, or autoimmune diseases can be provided.

Abstract: Provided are cortical interneurons and other neuronal cells and in vitro methods for producing such cortical interneurons and other neuronal cells by the directed differentiation of stem cells and neuronal progenitor cells. The present disclosure relates to novel methods of in vitro differentiation of stem cells and neural progenitor cells to produce several type neuronal cells and their precursor cells, including cortical interneurons, hypothalamic neurons and pre-optic cholinergic neurons. The present disclose describes the derivation of these cells via inhibiting SMAD and Wnt signaling pathways and activating SHH signaling pathway. The present disclosure relates to the novel discovery that the timing and duration of SHH activation can be harnessed to direct controlled differentiation of neural progenitor cells into either cortical interneurons, hypothalamic neurons or pre-optic cholinergic neurons.

Abstract: In certain aspects, the present invention provides methods for inducing a stable gene modification of a target nucleic acid via homologous recombination in a primary cell, such as a primary blood cell and/or a primary mesenchymal cell. In certain other aspects, the present invention provides methods for enriching a population of genetically modified primary cells having targeted integration at a target nucleic acid. The methods of the present invention rely on the introduction of a DNA nuclease such as a Cas polypeptide and a homologous donor adeno-associated viral (AAV) vector into the primary cell to mediate targeted integration of the target nucleic acid. Also provided herein are methods for preventing or treating a disease in a subject in need thereof by administering to the subject any of the genetically modified primary cells or pharmaceutical compositions described herein to prevent the disease or ameliorate one or more symptoms of the disease.

Abstract: A method for inducing reprogramming of a cell of a first type which is not a non-hepatocyte (non-hepatocyte cell), into a cell with functional hepatic drug metabolizing and transporting capabilities, is disclosed. The non-hepatocyte is induced to express or overexpress hepatic fate conversion and maturation factors, cultured in somatic cell culture medium, hepatocyte cell culture medium and hepatocyte maturation medium for a sufficient period of time to convert the non-hepatocyte cell into a cell with hepatocyte-like properties. The iHeps induced according to the methods disclosed herein are functional induced hepatocytes (iHeps) in that they express I and II drug-metabolizing enzymes and phase III drug transporters and show superior drug metabolizing activity compared to iHeps obtained by prior art methods. The iHeps thus provide a cell resource for pharmaceutical applications.

Abstract: A method of radiation-free hematopoietic stem cell (HSC) transplantation comprises administering to a mammalian subject one or two doses of 2 to 10 mg/kg body weight of a purine base analog, such as 6TG as a pre-conditioning step. The method further comprises engrafting into the subject hypoxanthine-guanine phosphoribosyltransferase (HPRT)-deficient donor HSCs within 48 to 72 hours of the pre-conditioning step; and administering to the subject about 1 to 5 mg/kg of the purine base analog every two to four days for two to eight weeks following the engrafting step. The method is performed in the absence of pre-conditioning via radiation. The subject is therefore not treated with myeloablative radiation in preparation for transplantation, and thus the subject is free of myeloablative radiation-induced toxicity.

Abstract: The present application relates to a non-human mammal model of a human neurodegenerative disorder, methods of producing the non-human mammal model, and methods of using the non-human mammal model to identify agents suitable for treating a neurodegenerative disorder. The present application also relates to methods of treating neurodegenerative disorders and restoring normal brain interstitial potassium levels.

Abstract: The present invention relates to an in vitro method for identifying a skin wound in an individual as being a non-healing skin wound or healing skin wound, in vitro methods for monitoring the healing of a skin wound in an individual, methods for screening for compounds suitable for modulating skin wound healing, as well as kits related thereto.

Abstract: Disclosed herein are methods for generating universal MHC/HLA-compatible hematopoietic progenitor cells and methods for generating custom patient-specific MHC/HLA-compatible hematopoietic progenitor cells. Compositions comprising the universal and custom hematopoietic progenitor cells and therapeutic applications thereof are also disclosed.

Abstract: The invention relates to a method for the cleavage of a solid phase-bound polypeptide from the solid phase, the method comprising contacting the solid phase, to which the polypeptide is bound, with a composition consisting essentially of trifluoroacetic acid and 1,2-ethanedithiol, at a temperature in the range of about 23° C. to about 29° C.

Abstract: Described herein is a chimeric antigen receptor (CAR) platform with the ability to (a) serve as an ON/OFF switch (with the ability for tenability/titrability), (b) sense multiple antigens and perform logic computations, and/or (c) independently regulate multiple signaling pathways. The compositions provided herein permit the degree of control and discrimination necessary to optimize CAR T cell therapy. Also described herein are cells comprising such compositions and the use of these compositions and/or cells in the treatment of cancer.

Abstract: Disclosed are compositions and methods for targeted treatment of CD123-expressing cancers. In particular, recombinant antibodies are disclosed that are able to engage T-cells to destroy CD123-expressing malignant cells.

Abstract: In order to improve the efficiency of gene introduction in CAR therapy employing a transposon method, provided is a method for preparing genetically-modified T cells expressing chimeric antigen receptor, comprising: (1) a step of preparing non-proliferative cells which are obtained by stimulating a group of cells comprising T cells using an anti-CD3 antibody and an anti-CD28 antibody followed by a treatment for causing the cells to lose their proliferation capability; (2) a step of obtaining genetically-modified T cells into which a target antigen-specific chimeric antigen receptor gene has been introduced using a transposon method; (3) a step of mixing the non-proliferative cells prepared by step (1) with the genetically-modified T cells obtained by step (2), and co-culturing the mixed cells while stimulating the mixed cells using an anti-CD3 antibody and anti-CD28 antibody; and (4) a step of collecting the cells after culture.

Abstract: Provided herein are extracellular vesicle (EV) (a.k.a. exosome) compositions for specifically targeting the delivery of a therapeutic agent to particular cells and/or tissues in a subject, as well as methods of making and methods of using said compositions. The compositions and methods disclosed herein are useful for targeted drug delivery in the treatment of diseases in which a cell surface receptor is overexpressed, such as, for example, cancer.

Abstract: The present invention provides a chimeric antigen receptor (CAR), comprising an extracellular part, at least one intracellular signaling domain, and at least one transmembrane domain, wherein the extracellular part of said CAR comprises a) at least one antigen binding domain, and b) at least one cytokine receptor activating or blocking domain. The invention also provides isolated nucleic acid molecule(s) encoding for the said CAR, a cell comprising said nucleic acid molecule(s), a cell expressing said CAR and therapeutic uses of said CAR.

Abstract: A population of genetically engineered T cells, comprising a disrupted Reg1 gene and/or a disrupted TGFBRII gene. Such genetically engineered T cells may comprise further genetic modifications, for example, a disrupted CD70 gene. The population of genetically engineered T cells exhibit one or more of (a) improved cell growth activity; (b) enhanced persistence; and (c) reduced T cell exhaustion, (d) enhanced cytotoxicity activity, (e) resistant to inhibitory effects induced by TGF-b, and (f) resistant to inhibitory effects by fibroblasts and/or inhibitory factors secreted thereby, as compared to non-engineered T cell counterparts.

Abstract: Described herein are compositions and methods of using placental stem cell recruiting factors, more specifically, isolated placental stem cell recruiting factors. In one embodiment, isolated placental stem cell recruiting factors are delivered to a site such as a diseased or injured organ and/or body part in an amount sufficient to recruit stem cells to the site.