Abstract: Affinity binding entities having TCRL binding domain and methods of their use are provided. More specifically these compositions bind HLA-A2/WT1+, HLA-A2/MAGE-A4, HLA-A2/MAGE-A9, HLA-A2/PAP or HLA-A2/TyrD+ cells and as such can be used in diagnostics and therapy.

Abstract: A method for culturing natural killer cells uses genetically modified T cells. The method for culturing natural killer cells, using genetically modified T cells enables the effective proliferation and production of natural killer cells from a smaller amount of source cells. In addition, the method enhances the cytolytic activity of natural killer cells. Therefore, the method for culturing natural killer cells, using genetically modified T cells may be suitable for various applications in commercializing cell therapy products. Further, the natural killer cells produced by the culturing method can be useful as a cell therapy product.

Abstract: The present invention relates to an engineered immune cell endowed with CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Abstract: Methods for preparing T cell populations useful for a variety of purposes requiring a highly active, long-lived T cell population. The T cell populations are enriched for: naive T cells (TN), memory stem cells (TSCM) and central memory T cells (TCM). These cell populations can be derived from peripheral blood mononuclear cells (PBMC) by both: 1) depleting unwanted cell populations such as CD14 expressing myeloid cells and CD25 expressing cells; and 2) enriching for CD62L expressing memory and naive T cells.

Abstract: The present disclosure provides a method for generating progenitor T cells from stem and/or progenitor cells comprising exposing the stem and/or progenitor cells to Notch ligand Delta-like-4 (DL4) and vascular adhesion molecule 1 (VCAM-1) under conditions suitable to generate progenitor T cells. The method provided is suitable for in vitro and in vivo pro-T cell generation. In vitro, the pro-T cells are generated under serum-free conditions. Cells produced using the method are provided as well as methods of using same.

Abstract: The present invention relates to an engineered immune cell endowed with CD22 Chimeric Antigen Receptors (CD22 CAR) with a deletion in the TRAC gene that is able to redirect immune cell specificity and reactivity toward selected tumor cells. The engineered immune cells endowed with such CARs are particularly suited for treating relapsed refractory CD22 expressing cancers.

Abstract: The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.

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: Methods of treating melanomas refractory to other therapies using tumor infiltrating lymphocytes are disclosed.

Abstract: Provided is a gRNA targeting HPK1 and a method for editing HPK1 gene. The method can knock out the T cell HPK1 gene, enhance the T cell killing activity, increase the Th1 cytokine level of peripheral blood mononuclear cells, and knock out of the T cell HPK1 gene can also down-regulate the expression of PD-1 and TIM3 on the T cell surface and can inhibit the T cell depletion.

Abstract: Proposed are a three-dimensional structuring method of cells and a three-dimensional structuring system of cells capable of efficiently bonding multiple cell clusters in a three-dimensional direction, pursuant to their growth, while ensuring safety. A plurality of fibers, in which one end of each of the fibers is held by a flat plate, are inserted together with the flat plate into a flow path through which a culture solution is supplied, a plurality of cell clusters are placed in the flow path upon causing the cell clusters to run with a liquid flow of the culture solution, and each of the cell clusters is cultured by being stacked on an outer surface of each of the fibers with the flat plate as a growth origin.

Abstract: Disclosed herein are cells that are immunoinhibitory cell, which cells recombinantly express a dominant negative form of an inhibitor of a cell-mediated immune response of the cell. In certain embodiments, the immunoinhibitory cell is a regulatory T cell. In another aspect, provided herein is a regulatory T cell that recombinantly expresses a dominant negative form of an inhibitor of a regulatory T cell-mediated immune response. The cells can be sensitized to an antigen that is the target of a pathologic immune response associated with an immune-mediated disorder. Additionally provided are methods of using such cells to treat an immune-mediated disorder in a subject in need thereof.

Abstract: The present invention relates to an in vitro culture of haematopoietic cells, wherein said haematopoietic cells differentiate to form granulocytes characterised by the ability to kill cancer cells. The invention also relates to said granulocytes, methods for identifying said haematopoietic cells and granulocytes, compositions and kits comprising the same, as well as uses of the same for treating cancer.

Abstract: The invention relates to an in vitro method to generate T cell progenitors, comprising the step of culturing CD34+ cells in a medium containing TNF-alpha and/or an antagonist of the Aryl hydrocarbon/Dioxin receptor, in particular StemRegenin 1 (SR1), in presence of a Notch ligand and optionally a fibronectin fragment.

Abstract: The methods of the invention employ targeted magnetic particles, preferably targeted nanomagnetic particles, and targeted buoyant particles such as buoyant microparticles and microbubbles. Among the benefits of the invention is the ability to combine targeted magnetic particles with differentially targeted buoyant particles to achieve separation of two or more specifically cell targeted populations during the same work flow.

Abstract: Provided herein are CRIS-PR/Cas9 complexes and methods of using same.

Abstract: The present invention relates to pharmaceutical compositions with isolated and treated whole blood cells or Peripheral Blood Mononuclear Cells (PBMCs) as well as such pharmaceutical compositions for use in the prevention and/or treatment of organ or cell graft rejection in a human graft recipient.

Abstract: A composition and a method for generating clinically safe NK cells derived from non-fully differentiated stem cells are provided. The non-fully differentiated stem cells are co-cultured with endogenous NK cells isolated from adipocyte-containing tissue to generate a high percentage of clinically safe NK cells, where anti-tumor activity of the clinically safe NK cells in vitro is similar to that of endogenous NK cells. Optimized Production of the clinically safe autologous NK cells from stem cells provides platform for treating cancer patients by applying an effective adoptive immunotherapy ranging from the early to terminal stages.

Abstract: The present invention relates to oncolytic vaccinia viruses which have been modified to promote anti-tumor immunity and/or reduce host immunity and/or antibody response against the virus. It is based, at least in part, on the discovery that oncolytic vaccinia virus (i) bearing a genome deletion of a gene that reduces T cell immunity (interleukin-18 binding protein); (ii) treated with a sialidase enzyme which is believed to reduce TLR2 activation and therefore the antibody response; (iii) carrying a gene that enhances cytotoxic T lymphocyte induction (e.g., TRIF) and/or (iv) reduces tumor myeloid-derived suppressor cells by reducing prostaglandin E2 reduces tumor growth. Accordingly, the present invention provides for immunooncolytic vaccinia viruses and methods of using them in the treatment of cancers.

Abstract: In some embodiments, marrow-infiltrating lymphocytes (“MILs”) comprising a chimeric antigen receptor (“CAR”) are provided. In some aspects, the embodiments relate to a method for making a recombinant MIL, comprising obtaining bone marrow comprising MILs; and transfecting, transforming, or transducing the MILs with a nucleic acid encoding a chimeric antigen receptor. In some aspects, the embodiments relate to a method for treating a condition in a subject, comprising administering to the subject a MIL comprising a CAR.

Abstract: Methods of treating melanomas refractory to other therapies using tumor infiltrating lymphocytes are disclosed. Also disclosed is the use of IP-10 as a biomarker for predicting treatment efficacy.

Abstract: The present invention relates to the field of immunology and to methods for inducing an M1/Th1 dominated immune response in an M2 macrophage dominated and/or Th2/Treg dominated human patient or animal. These methods are useful for developing therapies for treating or preventing M2 macrophage mediated and/or Th2/Treg mediated disease states.

Abstract: The invention provides compositions and methods for adoptive T cell therapy in treating a variety of disorders including cancer, infections, and autoimmune disorders. In one embodiment, the invention provides a universal immune receptor that comprises a protein or peptide tag, such as a SpyCatcher or a SpyTag moiety, bound to an extracellular hinge region, a transmembrane domain, and an intracellular domain for T cell activation.

Abstract: Provided herein are immune cells expressing antigenic receptors, such as a chimeric antigen receptor and a T cell receptor. Further provided herein are methods of treating immune-related disorder by administering the antigen-specific immune cells.

Abstract: The present invention relates to a cell which comprises a chimeric antigen receptor (CAR) and a signal transduction modifying protein, selected from one of the following: (i) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM), but lacks a kinase domain; (ii) a truncated protein which comprises an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM) but lacks a phosphatase domain; (iii) a fusion protein which comprises (a) an SH2 domain from a protein which binds a phosphorylated immunoreceptor tyrosine-based activation motif (ITAM) or from a protein which binds a phosphorylated immunoreceptor tyrosine-based inhibition motif (ITIM); and (ii) a heterologous domain.

Abstract: Methods of analyzing a biological fluid to determine an expected therapeutic benefit of the fluid include determining amounts of components within the biological fluid. Comparisons of a first component of the biological fluid relative to another component of the biological are made to characterize a therapeutic effect of the biological fluid.

Abstract: The present invention relates to a method for determining the potency of a supernatant of a mammalian cell culture to be used in the treatment of an inflammatory condition.

Abstract: Compositions comprising and methods for the treatment of cancer using a neoTCR based cell therapy with a CD8 expression construct.

Abstract: The present disclosure provides methods of preparing tumor infiltrating cells engineered to express a pro-inflammatory polypeptide. The pro-inflammatory polypeptide is expressed from the tumor infiltrating cell to counter a generally immunosuppressive state in and around tumors resulting from an imbalance between the number and activation state of immune effector cells versus those of suppressor cells. Delivering the proinflammatory polypeptide via expression from the TICs, as distinct from systemic administration, reduces side effects from increased inflammation at sides remote from a tumor to be treated.

Abstract: Disclosed herein is a genetically-modified cell comprising in its genome a modified human T cell receptor alpha constant region gene, wherein the cell has reduced cell-surface expression of the endogenous T cell receptor. The present disclosure further relates to methods for producing such a genetically-modified cell, and to methods of using such a cell for treating a disease in a subject.

Abstract: An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is disclosed. Methods of generating same and using same are also disclosed.

Abstract: Provided herein are methods of treating acute myeloid leukemia (AML) and multiple myeloma (MM) by administering an effective amount of a cell population comprising natural killer cells, wherein the cell population comprising natural killer cells is produced by a three-stage method comprising culturing a population of hematopoietic stem or progenitor cells in media comprising stem cell mobilizing factors, e.g., three-stage methods of producing NK cells in media comprising stem cell mobilizing factors starting with hematopoietic stem or progenitor cells from cells of the placenta, for example, from placental perfusate (e.g., human placental perfusate) or other tissues, for example, umbilical cord blood or peripheral blood. Further provided herein are methods of using the NK cells produced by the three-stage methods provided herein to suppress the proliferation of acute myeloid leukemia cells.

Abstract: An objective of the present invention is to provide vectors for conveniently and efficiently producing ES-like cells in which foreign genes are not integrated into the chromosome. The present inventors discovered methods for producing ES-like cells from somatic cells using chromosomally non-integrating viral vectors. Since no foreign gene is integrated into the chromosome of the produced ES-like cells, they are advantageous in tests and research, and immunological rejection and ethical problems can be avoided in disease treatments.

Abstract: The present invention concerns methods of generating CTLs that are able to target at least one antigen from two or more viruses. The method includes exposing mixtures of peptides for different antigens to the same plurality of PBMCs and, at least in certain aspects, expanding the cells in the presence of IL4 and IL7.

Abstract: Disclosed herein are chimeric antigen receptor effector cells (CAR-ECs) and CAR-EC switches. The switchable CAR-ECs are generally T cells. The one or more chimeric antigen receptors may recognize a peptidic antigen on the CAR-EC switch. The CAR-ECs and switches may be used for the treatment of a condition in a subject in need thereof.

Abstract: The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising an extracellular domain comprising an antigen binding domain, a transmembrane domain, and, an intracellular domain wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein X1 is an amino acid X2 is an amino acid X3 is an amino acid and X4 is V or I.

Abstract: The present invention describes a method for treating cancer comprising adoptive transfer of tumor antigen specific CD8+ T cells and an oncolytic virus vaccine targeting the same antigen.

Abstract: The present invention includes a method of suppressing systemic immune response in a subject, the method comprising topically administering a pharmaceutically effective amount of a vitamin D analog to a subject in need thereof. The present invention further includes a method of treating an autoimmune disease in a subject, the method comprising topically administering a pharmaceutically effective amount of a vitamin D analog to a subject in need thereof.

Abstract: A method of generating an isolated population of non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, the cells being tolerance inducing cells and/or endowed with anti-disease activity, and capable of homing to the lymph nodes following transplantation is disclosed. The method comprising: (a) providing a population of at least 70% memory T cells; (b) contacting the population of memory T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing the cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising the Tcm phenotype. Cells generated by the method, pharmaceutical compositions and methods of treatment are also disclosed.

Abstract: A method of treating a patient who has hepatocellular carcinoma (HCC), colorectal carcinoma (CRC), glioblastoma (GB), gastric cancer (GC), esophageal cancer, NSCLC, pancreatic cancer (PC), renal cell carcinoma (RCC), benign prostate hyperplasia (BPH), prostate cancer (PCA), ovarian cancer (OC), melanoma, breast cancer (BRCA), CLL, Merkel cell carcinoma (MCC), SCLC, Non-Hodgkin lymphoma (NHL), AML, gallbladder cancer and cholangiocarcinoma (GBC, CCC), urinary bladder cancer (UBC), and uterine cancer (UEC) includes administering to said patient a composition containing a population of activated T cells that selectively recognize cells in the patient that aberrantly express a peptide.

Abstract: Provided are methods and kits, e.g.; for testing the immune status of patients with chronic inflammatory diseases by measuring the TCR zeta chain (CD247) expression levels, and in particular a method and a kit for testing the selective downregulation of TCR zeta chain expression in T cells, NK cells, or NKT cells. Zeta chain expression is measured using antibodies directed against the intracellular zeta chain region, and these levels are compared with the expression levels of other T cell receptor subunits and NK cell markers. Provided are methods for determining diabetes complications in a diabetic patient. Further provided are kits for diagnosis, prognosis, and monitoring of same.

Abstract: Methods for preparing and using collagen extracts and collagen scaffolds are provided. Additionally methods and related kits for the repair of articular tissue using the collagen material are provided.

Abstract: Methods for generating/expanding populations of immune cells comprising immune cells specific for an Epstein Barr Virus (EBV) lytic antigen are disclosed, the methods comprising stimulating immune cells specific for an EBV lytic antigen by contacting peripheral blood mononuclear cells (PBMCs) with: (i) one or more peptides corresponding to all or part of one or more EBV lytic antigens; or (ii) antigen presenting cells (APCs) presenting one or more peptides corresponding to all or part of one or more EBV lytic antigens. Also disclosed are populations of immune cells comprising immune cells specific for an EBV lytic antigen expanded according to such methods, and uses thereof.

Abstract: The present invention pertains to antigen recognizing constructs against tumor associated antigens (TAA), in particular the TAA Serine protease inhibitor Kazal-type 2 (SPINK2). The invention in particular provides novel T cell receptor (TCR) based molecules which are selective and specific for the tumor expressed antigen of the invention. The TCR of the invention, and SPINK2 binding fragments derived therefrom, are of use for the diagnosis, treatment and prevention of SPINK2 expressing cancerous diseases. Further provided are nucleic acids encoding the antigen recognizing constructs of the invention, vectors comprising these nucleic acids, recombinant cells expressing the antigen recognizing constructs and pharmaceutical compositions comprising the compounds of the invention.

Abstract: The invention provides immunomodulatory pharmaceutical compositions that include a synthetic peptide and one or more immune tolerance enhancers.

Abstract: Methods and compositions are provided for treating a subject for aging-associated conditions, e.g., cognitive impairment conditions. Aspects of the methods include administering a young plasma-comprising blood product to an individual in need thereof, e.g., an individual suffering from or at risk of developing the aging-associated condition, e.g., aging-associated cognitive impairment. Also provided are compositions and kits thereof that find use in practicing methods of the invention.

Abstract: Labeled nucleotide analogs comprising at least one avidin protein, at least one dye-labeled compound, and at least one nucleotide compound are provided. The analogs are useful in various fluorescence-based analytical methods, including the analysis of highly multiplexed optical reactions in large numbers at high densities, such as single molecule real time nucleic acid sequencing reactions. The analogs are detectable with high sensitivity at desirable wavelengths. They contain structural components that modulate the interactions of the analogs with DNA polymerase, thus decreasing photodamage and improving the kinetic and other properties of the analogs in sequencing reactions. Also provided are nucleotide and dye-labeled compounds of the subject analogs, as well as intermediates useful in the preparation of the compounds and analogs. Compositions comprising the compounds, methods of synthesis of the intermediates, compounds, and analogs, and mutant DNA polymerases are also provided.

Abstract: Graft-versus-host disease (GVHD) is a lethal complication of allograft transplantation. The current strategy of using immunosuppressive agents to control GVHD may cause general immune suppression and limit the effectiveness of allograft transplantation. Adoptive transfer of regulatory T cells (Treg) can prevent GVHD in rodents, indicating the therapeutic potential of Treg for GVHD in humans. However, the clinical application of Treg-based therapy is hampered by the low frequency of human Treg and the lack of a reliable model to test their therapeutic effects in vivo. Human alloantigen-specific Treg are generated from antigenically-naïve precursors in a large scale ex vivo using allogeneic activated B cells as stimulators. Here, a human allogeneic GVHD model is established in humanized mice to mimic GVHD after allograft transplantation in humans.

Abstract: This disclosure is directed to a method for scoring and ranking candidate HLA-compatible unrelated hematopoietic cell donors (URD) for patients with AML or myelodysplastic syndrome. Candidate donors are scored based on KIR/HLA allele and genotype combinations. The method disclosed herein permits ranking and selection of advantageous donors that predict improved clinical outcomes of hematopoietic stem cell transplantation.

Abstract: The present description relates to T-cell receptors (TCRs) binding to tumor-associated antigens (TAAs) for targeting cancer cells, T-cells expressing same, methods for producing same, and methods for treating cancers using same. In particular, the present description relates to TCRs and their variants that bind to HLA class I or II molecules with a peptide, such as IGF2BP3-001 have the amino acid sequence of KIQEILTQV (SEQ ID NO:1). The present description further relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present description relates to the immunotherapy of cancer. The present description 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.