Abstract: The present disclosure provides, in some embodiments, methods for culturing and expanding hematopoietic stem cells (HSPCs) comprising a genomic modification associated with clonal hematopoiesis (CH). These cultured and expanded HSPCs are used, in some embodiments, to identify genes that promote CH, to identify inhibitors of CH, and to inhibit CH.

Abstract: The presently disclosed subject matter provides uses of anti-B7H3 antibodies for treating cancers in the central nervous system (CNS), including tumors metastatic to CNS, and in particular leptomeningeal carcinomatosis.

Abstract: Provided herein are compositions, methods, and uses involving anti-Mucin-16 (MUC16) agents that immunospecifically bind an epitope of Mucin-16 (MUC16). Also provided herein are uses and methods for managing, treating, or preventing disorders, such as cancer and diseases associated with positive MUC16 expression.

Abstract: This invention provides methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, by administering a combination of at least one WT1 peptide, or cytotoxic T cells (CTLs) against a WT1-expressing cancer, and at least one checkpoint inhibitor. The at least one WT1 peptide can be administered to the subject by administering one or more agents to the subject resulting in delivery of one or more WT1 peptides and induction of an immune response against the WT1-expressing cancer. Examples of these WT1 delivery agents include: (i) an isolated WT1 peptide, (ii) a nucleic acid encoding the at least one WT1 peptide, and (iii) an immune cell comprising or presenting the at least one WT1 peptide or nucleic acid encoding the at least one WT1 peptide.

Abstract: The present invention relates to the field of adoptive immunotherapy. The invention provides methods for generating phenotypically defined, functional, and/or expandable T cells from pluripotent stem cells engineered through safe genetic modifications. The engineered cells may provide one or more of: 1) targeting a specific predetermined antigen expressed on the cell surface of a target cell in an HLA independent manner, 2) enhanced survival and functional potential 3) “off-the-shelf” T cells for administration to multiple recipients, eventually across immunogenic barriers, and/or 4) cytotoxic potential and anti-tumor activity.

Abstract: The presently disclosed subject matter provides for in vitro methods of inducing differentiation of human stem cells into midbrain dopamine neurons, and precursors thereof, and cells generated by such methods. The presently disclosed subject matter also provides for uses of such cells for treating neurodegenerative disorders.

Abstract: The presently disclosed subject matter provides cells comprising a Fas ligand (FasL) polypeptide and a cFLIP polypeptide. In certain embodiments, the cells further comprise an antigen-recognizing receptor (e.g., a chimeric antigen receptor (CAR) or a T cell receptor (TCR), or a TCR like fusion molecule). Also provided are uses of the cells for cell lysis of target cells expressing Fas, and for treating diseases or disorders, e.g., tumors.

Abstract: The present disclosure relates to methods for modulating (e.g., maintaining) pluripotency and self-renewal property of cells (e.g., stem cells) by blocking the non-canonical tricarboxylic acid (TCA) cycle (e.g. using an inhibitor of ATP citrate lyase (ACL) or acetate), and kits and compositions relating thereto.

Abstract: Provided are pharmaceutical compositions and methods of treating or preventing edema, using an anti-T cell agent, an anti-TGF-?1 agent, or an anti-angiotensin agent, preferably a combination of at least two such agents. The pharmaceutical compositions can be formulated for systemic or local administration, and are preferably administered topically.

Abstract: The present disclosure is directed to systems and methods for reconstructing biomedical images. A projection preparer may identify a projection dataset derived from a tomographic biomedical imaging scan. An encoder-decoder model may reconstruct reconstructing tomographic biomedical images from projection data. The encoder-decoder model may include an encoder. The encoder may include a first series of transform layers to generate first feature maps using the projection dataset. The encoder-decoder may include a decoder. The decoder may include a second series of transform layers to generate second features maps using the first feature maps from the encoder. The system may include a reconstruction engine executable on the one or more processors. The reconstruction engine may apply the encoder-decoder model to the projection dataset to generate a reconstructed tomographic biomedical image based on the second feature maps generated by the decoder of the encoder-decoder model.

Abstract: The present disclosure describes compositions and methods for increasing the abundance of commensal bacteria belonging to the order Clostridiales, including Blautia, Ruminococcus, Clostridium, Eubacterium, Holdemania and Dorea species, that are associated with reduced lethal GVHD and improved overall survival following bone marrow or hematopoietic stem cell transplant. The present disclosure, therefore, provides methods for reducing the likelihood, incidence or severity of GVHD by (1) avoiding the loss of endogenous beneficial species through antibiotic selection; (2) by administering a therapeutically effective amount of a composition comprising one or more Clostridiales associated with reduced GVHD to individuals who may lack or have lost those strains from their intestinal microbiota.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating a neoplasia (e.g., multiple myeloma). It relates to chimeric antigen receptors (CARs) that specifically target Fc Receptor-like 5 (FcRL5), e.g., domain 9 of FcRL5, and immunoresponsive cells comprising such CARs. The presently disclosed FcRL5-targeted CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: Disclosed herein are cells that are immune cells or precursor cells thereof, which cells recombinantly express a chimeric antigen receptor (CAR), and a dominant negative form of an inhibitor of a cell-mediated immune response of the immune cell, wherein the CAR binds to a cancer antigen. Also disclosed herein are T cells that recognize and are sensitized to a cancer antigen, which T cells recombinantly express a dominant negative form of an inhibitor of a T cell-mediated immune response. Additionally provided are methods of using such cells to treat cancer in a subject in need thereof.

Abstract: This invention provides peptides, immunogenic compositions and vaccines, and methods of treating, reducing the incidence of, and inducing immune responses to a WT1-expressing cancer, comprising heteroclitic peptides derived from the WT-1 protein.

Abstract: The presently disclosed subject matter provides antibodies or antigen-binding fragments thereof that bind to DLL3 and methods of using such antibodies or antigen-binding fragments thereof same.

Abstract: Disclosed is a method for increasing susceptibility of cancer cells to ionizing radiation by delivering to the cells a radiosensitizing agent that has one of the following properties: (a) it perturbs the process of chromosome segregation thereby increasing chromosome missegregation; or (b) it is an inhibitor of an agent that promotes faithful chromosome segregation induces numeric chromosome instability in said cells and this instability is induced substantially simultaneously with or closely prior to or closely after irradiating the cells. Examples of such radiosensitizing agent include inhibitors of one or more of the following: Kif2b, MCAK, MPS1, Eg5/Kinesin-5 5, Polo-like kinase 4, MCAK, Bub1 and Hec1. Such agents specifically target proteins involved in maintaining or promoting faithful chromosome segregation.

Abstract: The presently disclosed subject matter provides antibodies that mimic TCR recognition of HPV-derived epitopes presented by HLA class I molecules, antigen-recognizing receptors that target HPV-derived epitopes presented by HLA class I molecules, and methods of using such antibodies.

Abstract: The present disclosure relates to methods of treating a vascular malformation in a subject expressing a gain-of-function mutation in a PIK3CA gene comprising administering, to the subject, an effective amount of an agent that inhibits phosphoinositide 3-kinase (“PI3K”).

Abstract: The presently disclosed subject matter provides cells, compositions and methods for enhancing immune responses toward tumor. It relates to cells comprising: an antigen-recognizing receptor (e.g., a chimeric antigen receptor, a TCR, or a TCR like fusion molecule), a Fas ligand polypeptide (FasL), and a gene disruption of a Fas locus. The gene disruption of the Fas locus can improve the activity and/or efficiency of the cells. The presently disclosed cells, compositions, and methods can be used in allogeneic settings.

Abstract: The invention provides methods to inhibit or treat brain cancers by locally inhibiting expression or activity of growth factors or growth factor receptors.