Abstract: The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and/or survival of NK cells.

Abstract: The bioactive compounds of Ganoderma lucidum extract (GLE) responsible for anticancer activity were elucidated using NMR, X-ray crystallography and analogue derivatization, as well as anti-cancer activity studies. Structures of the seven most abundant GLE compounds are disclosed. Their selective efficacy against triple negative (TNBC) and inflammatory breast cancers (IBC) and other human cancer cell types (solid and blood malignancies) was shown, confirming potential their as anticancer agents.

Abstract: The present application provides chimeric antigen receptors (CARs) comprising an anchoring domain, such as a PDZ binding motif, which binds to a cell polarity protein. Also provided are poly nucleotides encoding the CARs, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a disease in a subject are also provided.

Abstract: In one aspect, a method of treating a subject having or at risk of having graft-versus-host disease (GvHD) generally includes administering to the subject a plurality of myeloid-derived suppressor cells (MDSCs) effective to ameliorate at least one symptom or clinical sign of graft-versus-host disease compared to a suitable control subject. In another aspect, a method of treating a tumor in a subject generally includes administering to the subject an anti-tumor therapy and co-administering to the subject an inflammasome inciting agent in an amount effective to increase inflammasome activation of MDSCs sufficiently to reduce suppressor function of the MDSCs.

Abstract: The present disclosure relates generally to methods for generating a pre-effector gene signature for determining the C cytotoxic effector potential of a preparation of chimeric antigen receptor (CAR) T cells comprising measuring single-cell gene expression data and endogenous T cell receptor (TCR) sequencing data of the preparation of CAR T cells. The present invention relates also to methods for determining the cytotoxic effector potential of a preparation of CAR T cells or a subset of CAR T cells therefrom as well as methods for treating a cancer in a subject in need thereof by administering a preparation of CAR T cells determined to have a cytotoxic effector potential.

Abstract: An exemplary embodiment of the present disclosure provides systems and methods for mapping a location of cell types within a tissue sample. The system may include one or more processors, a non-transient memory in communication with the one or more processors storing instructions that when executed by the one or more processors are configured to perform method steps. The method may include receiving a tissue sample, capturing image data of the tissue sample, extracting a plurality of nucleic molecules from the tissue sample, and generating spatially resolved transcriptomic data from the extracted plurality of cellular analytes. The method may include determining cell-type reference data and generating a feature map of the tissue sample that includes a final inferred cell type compositional map for each tissue region of the tissue sample based on the spatially resolved transcriptomics data, the cell-type reference data, and the mapping estimate of cell types.

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: The application provides modified immune effector cells wherein the DNA (cytosine-5)-methyltransferase 3A (DNMT3A)-mediated de novo DNA methylation of the cell genome is inhibited, and IL10 signaling pathway is enhanced. The application also provides related pharmaceutical compositions and the methods for generating such modified immune effector cells. The application further provides uses of such modified immune effector cells for treating diseases such as cancers, infectious diseases and autoimmune diseases.

Abstract: The disclosure relates to methods for characterizing and/or treating a subject having cancer, said methods comprising performing an assay to identify the nucleotides present at each of a set of single-nucleotide polymorphism (SNP) locations within the cytarabine (ara-C) pathway, assigning a genotype score for the identified nucleotides of each SNP, and characterizing the subject having cancer based on the summation of the assigned genotype scores. In some embodiments, treatment is administered based upon the characterization of the subject, according to the methods described herein.

Abstract: The application relates to a chimeric receptor that targets CD33 and allows activation of the co-stimulatory pathway without binding the natural ligand. The application also relates to polynucleotides that encode the chimeric receptor, vectors, and host cells comprising the chimeric receptor. The application also relates to methods for preparing host cells comprising a chimeric antigen receptor in order to improve the in vivo persistence of the chimeric antigen receptor host cells.

Abstract: The invention generally relates to methods of treating viral infections using known drugs and pharmaceutical compositions comprising same. More specifically, the disclosed methods are useful for the treatment of viral infections that are enveloped viruses. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: The application provides chimeric antigen receptors (CARs) that target splice variants of the extracellular matrix proteins tenascin C (TNC) and procollagen 11A1 (Col11A1), and their uses in tumor immunotherapy. The application also provides polynucleotides and vectors that encode the chimeric antigen receptors, as well as host cells comprising the chimeric antigen receptors. The application also provides methods for preparing host cells comprising the chimeric antigen receptors and methods for treating patients using the modified host cells.

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 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: The invention provides methods for overcoming glucocorticoid resistance of cancers by inhibition of CASP1. Also disclosed are diagnostic methods for determining glucocorticoid resistance potential by measuring expression level or promoter methylation status of CASP1 gene and/or NLRP3 gene.

Abstract: Provided herein are compositions and methods for accurate and scalable Primary Template-Directed Amplification (PTA) nucleic acid amplification and sequencing methods, and their applications for research, diagnostics, and treatment.

Abstract: The present disclosure relates to chemical compounds that modulate pantothenate kinase (PanK) activity for the treatment of metabolic disorders (such as diabetes mellitus type II), neurologic disorders (such as pantothenate kinase-associated neurodegeneration), pharmaceutical compositions containing such compounds, and their use in treatment. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

Abstract: Methods and compositions using an inhibitor of EGFR signaling for prevention or an inhibitor of EGFR signaling and a nucleic acid molecule encoding an atonal-associated factor for treatment of hearing loss are described.

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 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: The present disclosure provides chimeric MyD88 receptors. Also provided are polynucleotides encoding the chimeric MyD88 receptors, vectors comprising the polynucleotides encoding the chimeric MyD88 receptors, and cell compositions comprising the chimeric MyD88 receptors, polynucleotides and/or vectors. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a disease in a subject are also provided.

Abstract: The present invention provides methods of genetically modifying an immune cell such that the immune cell expresses a transgene in an activation dependent manner. The application also provides genetically modified immune cells prepared using such methods, and the uses of the genetically modified immune cells in immunotherapy (e.g., adoptive cell therapy) for treatment of a disease such as cancer, autoimmune disease or infectious disease.