Abstract: The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs 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: Handheld devices and methods that integrate wide-field dermoscopy with reflectance confocal microscopy for non-invasive simultaneous capture of wide-field color images of the skin surface and images of the sub-surface cellular structure.

Abstract: The present disclosure relates generally to complexes comprising an interleukin-15 (“EL-15”) polypeptide chain non-covalently bonded to an IL-15 receptor ?-Fc fusion polypeptide (“IL-15R?-Fc”), and multimers (e.g., trimers) thereof. The complexes of the present technology are useful in methods for enhancing immune cell function and immunotherapy in a patient in need thereof. Also provided herein are methods for preventing or treating a disease or condition in which enhancing IL-15-mediated function is beneficial (such as cancer, infectious diseases, immunodeficiencies and leukopenia) in a patient in need thereof.

Abstract: The present invention relates to methods for treating brain metastasis by inhibiting gap junction functionality. It is based, at least in part, on the discovery that cancer cells expressing Protocadherin 7 and Connexin 43 form gap junctions with astrocytes that promote the growth of brain metastases, and that inhibition of Protocadherin 7 and/or Connexin 43 expression in cancer cells reduce progression of brain metastases. It is further based on the discovery that treatment with gap junction inhibitors tonabersat and meclofenamate inhibited progression of brain metastatic lesions and enhanced the anti-cancer activity of the conventional chemotherapeutic agent, carboplatin.

Abstract: The present invention relates to methods and compositions for reducing the risk and severity of vancomycin-resistant Enterococci infection or colonization. It is based, at least in part, on the discovery that a restricted fraction of the gut microbiota, including the bacteria Clostridium scindens and/or the bacteria Blautia producta contribute substantially to resistance against vancomycin-resistant Enterococci infection or colonization. Without being bound by any particular theory, it is believed that this is achieved through the biosynthesis of secondary bile acids in the case of Clostridium scindens.

Abstract: The present disclosure relates generally to immunoglobulin-related compositions (e.g., heterodimeric trivalent/tetravalent multispecific antibodies) that specifically bind to three or four distinct target antigens. The immunoglobulin-related compositions described herein are useful in methods for detecting and treating cancer in a subject in need thereof.

Abstract: The present invention relates generally to the fields of oncology, virology and immunotherapy. More particularly, it concerns the use of a recombinant modified vaccinia Ankara (MVA) virus comprising an MVA harboring a human Fms-like tyrosine kinase 3 ligand (hFlt3L) (MVA-hFtl3L). The foregoing vaccinia Ankara (MVA) virus can be delivered to tumor cells of a subject afflicted with a malignant solid tumor, to treat the tumor. In a related aspect, the present disclosure concerns a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MV At.E3L) modified to express human Fms-like 5 tyrosine kinase 3 ligand (hFlt3L) isolated, suitable for use as an immunotherapeutic agent against a malignant solid tumor.

Abstract: Disclosed is a method for enhancing tumor response to chemotherapy, the method comprising administering a short-acting anti-angiogenic agent (AAA) capable of activating ASMase to a subject afflicted with a solid tumor, and thereby creating a time interval of increased susceptibility of said tumor to one or more chemotherapeutic agents, followed by administration of at least one chemotherapeutic agent within the interval. The interval can be defined in terms of a short-duration activation of ASMase signaling by the AAA. Disclosed are also methods for predicting the tumor response in a patient afflicted with a solid tumor to a chemotherapeutic agent, using as an indicator of the response ASMase level or activity (or ceramide level) in the patient following the administration of the chemotherapeutic agent to the patient, or dynamic IVIM based DW-MRI to measure perfusion alterations following administration of the chemotherapeutic agent.

Abstract: An anti-myeloid-derived suppressor cells agent (“anti-MDSCs agent”) and a bacteriochlorophyll derivative (hereinafter “Bchl-D) for use in combination therapy for cancer, wherein the anti-MDSC agent and the Bchl-D are administered sequentially and the administration of the Bchl-D is followed by photodynamic therapy (PDT) or vascular targeted PDT (VTP).

Abstract: Truncated triterpene saponin analogues containing a trisaccharide or tetrasaccharide ester are disclosed. Also disclosed are pharmaceutical compositions comprising truncated saponin analogues and synthetic methods of producing the truncated saponin analogues. Another aspect of the present application relates to a method for immunizing a subject, comprising administering to the subject the pharmaceutical composition comprising a minimal saponin analogue and an antigen.

Abstract: The presently disclosed subject matter provides methods and compositions for treating myeloid disorders (e.g., acute myeloid leukemia (AML)). It relates to immunoresponsive cells bearing antigen recognizing receptors (e.g., chimeric antigen receptors (CARs)) targeting AML-specific antigens.

Abstract: The present disclosure relates generally to methods for preventing, ameliorating or treating leukemia. In particular, the present disclosure relates to administering a therapeutically effective amount of at least one agent to reduce the expression of synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP) to a subject diagnosed with, or at risk for acute myeloid leukemia (AML).

Abstract: The present invention provides immunoresponsive cells, including T cells, cytotoxic T cells, regulatory T cells, and Natural Killer (NK) cells, expressing an antigen recognizing receptor and an inhibitory chimeric antigen receptor (iCAR). Methods of using the immunoresponsive cell include those for the treatment of neoplasia and other pathologies where an increase in an antigen-specific immune response is desired.

Abstract: The disclosure relates to novel selective Grp94 inhibitors, compositions comprising an effective amount of such compounds, and methods to treat or prevent a condition, such as cancer, comprising administering to an animal in need thereof an effective amount of such compounds.

Abstract: The instant disclosure provides antibodies that specifically bind to human CTLA-4 and antagonize CTLA-4 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: A genomic data translation system can be configured to process next-generation sequencing information. The system can receive an output file including raw genome data. The system can parse the output file to determine segments corresponding to individual chromosomes. The system can identify ranges of nucleotides and determine the first set of genes included in a human reference genome listing that fall within the ranges. The system can also maintain a gene list of genes, and determine a matched set of genes that are included in the gene list and the first set of genes. The system can generate a configurable text string including non-configurable regions and configurable regions. The configurable regions can be populated with text based on the raw genomic data, a set of translation rules, and a set of translation text strings.

Abstract: In some aspects the present invention provides methods for the treatment of B-cell lymphomas. Some such methods involve administration of HVEM ectodomain polypeptides, anti-HVEM antibodies, or anti-BTLA antibodies to subjects in need thereof. Some such methods involve use of CAR T cells, such as CD19-specific CAR T cells. The present invention also provides compositions useful in such methods. These and other embodiments of the present invention and described further herein.

Abstract: The present invention provides biomarkers for sensitive, specific, accurate and quantitative diagnosis and assessment of chronic hypoxia. In particular, the present invention provides 2-hydroxyglutarate as a biomarker that is differentially produced in chronic hypoxia. Furthermore, embodiments of the invention are able to differentiate between chronic and acute hypoxia. Assays for levels of 2-hydroxyglutarate may be used alone or in conjunction with additional biomarkers of hypoxia to increase the precision of analysis. In particular embodiments of the invention, the level of 2-hydroxyglutarate and at least one second biomarker may be assayed to generate a hypoxic profile that can be compared to a reference or control profile, thereby diagnosing a subject as normoxic, chronically hypoxic, or acutely hypoxic.

Abstract: Described herein are systems and methods of training models to segment images. A device may identify a training dataset. The training dataset may include images each having a region of interest. The training dataset may include first annotations. The device may train, using the training dataset, an image segmentation model having parameters to generate a corresponding first segmented images. The device may provide the first segmented images for presentation on a user interface to obtain feedback. The device may receive, via the user interface, a feedback dataset including second annotations for at least a subset of the first segmented images. Each of the second annotations may label at least a second portion of the region of interest in a corresponding image of the subset. The device may retrain, using the feedback dataset received via the user interface, the image segmentation model.