Abstract: Provided is a method for producing a stem cell-derived lacrimal gland tissue, the method comprising isolating SSEA4 and CD104 double positive cells from a self-formed ectodermal autonomous multi-zone (SEAM) cell population derived from pluripotent stem cells and three-dimensionally culturing the isolated cells in a medium with epidermal growth factor (EGF) and a ROCK inhibitor to produce a cell population expressing a lacrimal gland-related protein. The present invention provides a lacrimal gland organoid produced from pluripotent stem cells including iPS cells and thus is very useful for cell-based regenerative therapy for lacrimal gland-related diseases and cell-based research on the diseases.

Abstract: Provided herein are methods and systems for targeted gene disruption (knock-out, missense mutation) and targeted gene knock-in in mammalian cells using base editors and guide RNAs (gRNAs) designed to target splice acceptor-splice donor sites. Also provided herein are universally acceptable genetically engineered cells comprising targeted disruptions in immunotherapy-related genes and comprising a CAR/TCR for therapeutic applications.

Abstract: The presents invention relates to a composition for manipulating an immune cell which is used for artificially manipulating an immune cell. More particularly, the present invention relates to a composition for manipulating an immune cell which is used for artificially manipulating an immune cell and a manipulated immune cell comprising an artificially modified immunity regulating gene and an artificial receptor which is produced using the composition, and use thereof.

Abstract: An immunotherapeutic composition is contemplated that comprises subject-derived peripheral blood mononuclear cells (PBMC) and at least one recombinant adenovirus subtype 5 (Ad5) comprising a deletion in an E1 gene region, a deletion in an E2b gene region, and a nucleic acid sequence encoding a peptide antigen, wherein the PBMC are exposed ex-vivo to the at least one Ad5 vector. Advantageously, the same PBMC composition may also be used to prepare modified NK cells, and especially modified NK include CIML NK cells, CENK cells and mCENK cells.

Abstract: A culture container for culturing lymphocytes includes an immobilized surface and a non-immobilized surface, wherein the culture container is formed of a gas permeable film, the immobilized surface and the non-immobilized surface are container inner surfaces facing each other, and anti-CD3 antibodies are immobilized in the immobilized surface at a concentration of 10 to 300 ng/cm2.

Abstract: The generation of antigen specific T cells by controlled ex vivo induction or expansion can provide highly specific and beneficial T cell therapies. The present disclosure provides T cell manufacturing methods and therapeutic T cell compositions which can be used for treating subjects with cancer and other conditions, diseases and disorders personal antigen specific T cell therapy.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: Methods of generating an autologous cellular vaccine comprising monocytes or neutrophils and an antigenic polypeptide or nucleotide encoding the antigenic polypeptide are provided. The antigen-loaded cell-based vaccine compositions made using these methods are also provided. Methods of using the antigen-loaded cell-based vaccine compositions are also provided and these vaccines may be used to treat cancer. Kits for carrying out the methods described herein are also provided.

Abstract: Disclosed are methods of preparing thymic emigrant cells in vitro, isolated or purified thymic emigrant cells prepared by the methods, and pharmaceutical compositions comprising the same. Further disclosed are methods of treating or preventing a condition in a mammal comprising administering the thymic emigrant cells or pharmaceutical compositions comprising the same to the mammal.

Abstract: Described herein are engineered antigen presenting cells that can be capable of modulating a target T-cell in a T-cell antigen specific manner. In some embodiments, the engineered APCs can include a modified antigen presentation pathway. Also described herein are methods of making and using the engineered antigen presenting cells.

Abstract: The present invention provides improved and/or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

Abstract: The present application discloses a method for inducing cells to gain characteristics of naïve stem cell state comprising culturing the cells in the presence of a MUC1* activator.

Abstract: The invention provides methods and compositions for administration of allogeneic lymphocytes as an exogenous source of CD4+ T cell help for endogenous, tumor-reactive CD8+ T cells.

Abstract: The instant disclosure provides antibodies that specifically bind to LAG-3 (e.g., human LAG-3) and antagonize LAG-3 function. Also provided are pharmaceutical compositions comprising these antibodies, nucleic acids encoding these antibodies, expression vectors and host cells for making these antibodies, and methods of treating a subject using these antibodies.

Abstract: This disclosure relates to growth media and environments for in vitro culturing of cells that produce or are capable of producing antibodies. In certain embodiments, the media comprises IL-6, fibronectin, and typically a saccharide. In certain embodiments, the disclosure contemplates cell culture compositions comprising IL-6 and fibronectin that are derived from proteins secreted from mesenchymal stromal/stem cells (MSCs). In certain embodiments, the disclosure contemplates enclosures comprising culture compositions disclosed herein that are in ambient air or optionally in an environment wherein oxygen is absent or at a low concentration.

Abstract: Cell culture systems and methods provide improved immunotherapeutic product manufacturing with greater scalability, flexibility, and automation. Cell culture systems are configured with interchangeable cartridges, allowing versatility and scalability. Systems are configured to have multiple connected cell culture chambers, which allows parallel processing of different types of cells. Gas-impermeable cell culture chambers and methods for generating cells in closed systems prevent contamination and user error. Methods for recycling cell culture medium provide additional efficiencies.

Abstract: This disclosure relates to the genetic modification of DNMT3A gene in immune cells. In certain embodiments, the modified immune cells may be used in adoptive T cells therapies to enhance immune responses against cancer or chronic infections. In certain embodiments, the disclosure relates to deleting, changing, or inserting nucleotides within the DNMT3A gene in immune cells, e.g., human CD8 T cells, such that the DNMT3A gene product does not function for methylation. In certain embodiments, modification of the DNMT3A gene provides an improvement in antigen-specific T cells functions and/or an enhancement of the longevity of the cells.

Abstract: This disclosure relates to methods of culturing and characterizing antibody secreting cells. In certain embodiments, this disclosure relates to methods of isolating antibody secreting cells, e.g., long lived plasma cells, replicating the isolated cells in growth media disclosed herein, and determining the nucleic acids sequences in the cells that encode the produced antibodies.

Abstract: Disclosed herein are non-myeloablative antibody-toxin conjugates and compositions that target cell surface markers, such as the CD34, CD45 or CD117 receptors, and related methods of their use to effectively conditioning a subject's tissues (e.g., bone marrow tissue) prior to engraftment or transplant. The compositions and methods disclosed herein may be used to condition a subject's tissues in advance of, for example, hematopoietic stem cell transplant and advantageously such compositions and methods do not cause the toxicities that are commonly associated with traditional conditioning methods.

Abstract: Polypeptides having target levels of C-terminal variants are described.