Abstract: Chimeric antigen receptor (CAR) with a binding domain that binds STEAP1 are disclosed. The CAR disclosed herein can be used in the treatment of prostate cancer, the Ewing family of tumors (EFT), bladder cancer, ovarian cancer, and rhabdomyosarcoma. The CAR disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

Abstract: Newborn screening for primary immunodeficiencies, cystinosis, and Wilson disease is described. The newborn screening can detect these disorders from dried blood spots already routinely collected at the time of birth. Early detection of these disorders will greatly improve patient outcome as each of them can be fatal once symptoms emerge.

Abstract: DNA hypomethylation as a predictive marker for cancer therapy is described. The susceptibility of hypomethylated cancers to particular treatments, for example to AKT inhibitors and anthracyclines is described. The described susceptibilities can be used to direct enrollment of subjects into appropriate clinical trials and to guide treatment selection and administration based on global DNA methylation level.

Abstract: Siderocalin-metal chelator combinations that bind metallic radioisotopes used in nuclear medicine with high affinity are described. The high affinity siderocalin-metal chelator combinations include a number of chelator backbone arrangements with functional groups that coordinate with metals. The siderocalin-metal chelator combinations can be used to deliver radionuclides for imaging and therapeutic purposes.

Abstract: Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Abstract: A method for analyzing an ability of target nucleic acid sequences to impact gene expression is described. In an embodiment, the method includes cloning the target nucleic acid sequences and associated barcode nucleic acid sequences into a plurality of plasmids, sequencing the plasmids to provide long-read sequencing information based on a target nucleic acid sequence of the target nucleic acid sequences and an associated barcode nucleic acid sequence, associating the target nucleic acid sequence with the associated barcode nucleic acid sequence based on the long-read sequencing information, transducing the plurality of plasmids into a plurality of cells, extracting DNA, total mRNA, and polysome-bound mRNA from the cells, sequencing the barcode nucleic acid sequences in the extracted DNA, total mRNA, and polysome-bound mRNA to provide short-read sequencing information, and analyzing the target nucleic acid sequences by comparing the long-read sequencing information and the short-read sequencing information.

Abstract: Provided herein are methods and compositions for overcoming resistance to and/or augmenting efficacy of Prostate specific membrane antigen (PSMA)-directed therapies in a subject. In some embodiments, the method comprises administering to the subject in need thereof an effective amount of at least one agent capable of modulating the expression of PSMA. The disclosure also is directed to a method for sensitizing a cancer to a PSMA-targeted therapeutic agent and/or a PSMA-targeted theranostic agent in a subject in need thereof. Also provided are methods and compositions for treating prostate cancer in a subject in need thereof.

Abstract: Compositions and methods for treatment of conditions associated with IDH1/2 mutation(s) are disclosed. The compositions and methods include administering an SRC inhibitor and a p70 S6 kinase/AKT (S6K/AKT) inhibitor. Examples of conditions associated with IDH1/2 mutation(s) include intrahepatic cholangiocarcinoma (ICC), oligodendrogliomas, astrocytomas, glioblastomas, leukemias, adenocarcinoma, gliomas, melanomas, oligoastrocytomas, invasive breast carcinoma, invasive ductal carcinoma, and myelodysplastic syndromes.

Abstract: Methods and compositions for modulating the myeloid arm of the immune system are described. The methods and compositions modulate the myeloid arm of the immune system by stimulating or inhibiting Sema4 and/or a PlexinD1 receptor. Stimulating Sema4 and/or a PlexinD1 receptor down-regulates or dampens the myeloid arm of the immune system while inhibiting Sema4 and/or a PlexinD1 receptor up-regulates or heightens the myeloid arm of the immune system. The ability to modulate the myeloid arm of the immune system provides many advances such as reducing immune-responsiveness to various forms of stress and enhancing immune responsiveness to physiological challenges.

Abstract: Siglec-8 antibodies and uses thereof are described. The Siglec-8 antibodies can be fully human and can be used for a variety of purposes, including in the research, diagnosis, and treatment of eosinophil and mast cell related disorders, such as asthma, rhinitis, dermatitis, eosinophilic gastrointestinal disorders, eosinophilic pneumonia, anaphylaxis, urticaria, eosinophilic cellulitis and fasciitis, Churg-Strauss syndrome, hematologic malignancies involving eosinophils or mast cells, and mastocytosis.

Abstract: Anti-CD33 antibodies are described. The anti-CD33 antibodies can bind within the V-set Ig-like domain or the C2-set Ig-like domain of CD33. Epitopes on the C2-set Ig-like domain can provide a “pan-binding” site, to which the cognate antibody will bind regardless of whether the CD33 molecule also contains the V-set domain (as in, for example, CD33FL) or not (as in, for example, CD33?E2). Alternative epitopes on the C2-set Ig-like domain are accessible for binding if the V-set domain is absent (e.g., as in CD33?E2). Antibodies that bind an epitope on the C2-set Ig-like domain (whether they exhibit pan or V-set absent binding) are directed at novel therapeutic targets and can increase therapeutic efficacy against CD33-related disorders. Also described are molecules comprising a binding-competent domain from at least one described anti-CD33 antibody, including scFvs, bi-specific antibody molecules, chimeric antigen receptors, and immunoconjugates. Methods of use are also provided.

Abstract: Provided are compositions and methods of T cell-based immunotherapies targeting hematologic malignancies that contain a mutation in the SF3BI protein.

Abstract: Targeted therapeutics for the treatment of cancers expressing FOLR1, MEGF10, HPSE2, KLRF2, PCDH19, and/or FRAS1 are described. The targeted therapeutics can include a chimeric antigen receptor (CAR) expressed by an immune cell or an antibody-targeted therapeutic. The targeted therapeutics can be used to treat a variety of cancers including solid tumors and blood cancers, such as CBFA2T3-GLIS2 acute myeloid leukemia (C/G AML).

Abstract: The present invention relates to a combination of sensors, a system and a method for monitoring incontinence and physiological parameters. The system includes a plurality of electrodes on an absorbent article including an absorbent core to be worn by a wearer being monitored, a device for electrical connection with the electrodes and for monitoring one or more electrical properties of the electrodes indicative of the occurrence of an incontinence event, an oxygen saturation sensor for monitoring the oxygen saturation of the blood of the wearer, and wherein the operation of the oxygen saturation sensor is controlled according to the body position of the wearer.

Abstract: Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and/or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and/or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Abstract: The present disclosure provides methods for detecting antigen-specific cells, such as T cells or B cells, using a proximity ligation assay (PLA) in which at least one of the PLA probes is a peptide-major histocompatibility (MHC) multimer or a B cell specific antigen bound to an oligonucleotide. Also provided are kits for use in such methods.

Abstract: Embodiments include engineered minicircle-producing bacterium with differential methylation capability, as well as kits and compositions comprising the bacterium. Further described are methods of using of the bacterium for producing differentially methylated minicircle DNA, and for improving transformation efficiency of exogenous DNA in intractable bacteria.

Abstract: A system generates a visualization that represents progression of a cancer genome. To generate the visualization, the system obtains a genetic dataset derived from cancer cell samples of a patient and clinical data associated with the patient. A genomic data structure is generated to represent the genetic dataset, and clinical event data structures are generated to represent each of a plurality of clinical events based on the clinical data. The visualization includes interactive elements that are populated based on the genomic data structure and the clinical event data structures. When a user input associated with a first interactive element is detected, the system displays information associated with the first interactive element based on the genomic data structure or the clinical event data structures.