Abstract: Systems and methods for multi-modal, multi-resolution deep learning neural networks for segmentation, outcomes prediction and longitudinal response monitoring to immunotherapy and radiotherapy are detailed herein. A structure-specific Generational Adversarial Network (SSGAN) is used to synthesize realistic and structure-preserving images not produced using state-of-the art GANs and simultaneously incorporate constraints to produce synthetic images. A deeply supervised, Multi-modality, Multi-Resolution Residual Networks (DeepMMRRN) for tumor and organs-at-risk (OAR) segmentation may be used for tumor and OAR segmentation. The DeepMMRRN may combine multiple modalities for tumor and OAR segmentation. Accurate segmentation is may be realized by maximizing network capacity by simultaneously using features at multiple scales and resolutions and feature selection through deep supervision. DeepMMRRN Radiomics may be used for predicting and longitudinal monitoring response to immunotherapy.

Abstract: Compounds having methyltransferase inhibitory activity are disclosed. The compounds have the structures The compounds disclosed are useful in the treatment of cancer and similar diseases associated with inappropriate methyltransferase activity.

Abstract: Described herein are chimeric Newcastle disease viruses comprising a packaged genome comprising a transgene encoding interleukin-12. The chimeric Newcastle disease viruses and compositions thereof are useful in combination with an antagonist of programmed cell death protein 1 (“PD-1”) or a ligand thereof in the treatment of cancer. In particular, described herein are methods for treating cancer comprising administering the chimeric Newcastle disease viruses in combination with an antagonist of PD-1 or a ligand thereof, wherein the chimeric Newcastle disease virus comprises a packaged genome comprising a transgene encoding interleukin-12.

Abstract: Described are embodiments of a scalable system for processing whole slide images (WSIs). The system may heavily utilize parallel processing on both central processing units (CPUs) and graphics processing units (GPUs). Images may be decoded on a GPU. Reads may be unbuffered with a low memory footprint. Compute Unified Device Architecture (CUD A) operations may be employed to eliminate many inefficiencies in traditional WSI processing libraries.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of T cell receptors (TCRs) and engineered immunoresponsive cells comprising the same. The novel TCR binds to an antigen in an HLA-independent manner. In certain embodiments, the novel TCR provides enhanced sensitivity for a target gene having a low expression level.

Abstract: The present disclosure relates generally to the fields of oncology, virology and immunotherapy. It concerns poxviruses, specifically the highly attenuated modified vaccinia virus Ankara (MVA), and a recombinant modified vaccinia Ankara virus with deletion of vaccinia virulence factor E3 (MVA?E3L), each further modified to express human Fms-like tyrosine kinase 3 ligand (Flt3L) or GM-CSF. The disclosure relates to use of the foregoing recombinant viruses as cancer immunotherapeutic agents. The foregoing recombinant poxviruses can also be used in combination with immune checkpoint blockade therapy.

Abstract: The present application relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, and intermediates thereto. The application also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds or compositions in the treatment of and immunization for infectious diseases.

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: 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 disclosure is directed to managing and accessing experiment data. A data processing system may generate a system identifier for each instance that leads to a generation of experiment data. A first segment may refer to a source entity, and may be used to differentiate identifiers generated by different source entities. This implementation may aim to provide an explicit representation of the data generation process while providing a glimpse on select metadata attributes, such as an individual species, sample class, and experimental technique used to generate the dataset. These constraints may prevent duplicates and may enable system-side associations among subjects, samples, aliquots, and experiments.

Abstract: A target may be tagged, and its position tracked to maintain the position of the target at the center (e.g., zero region) of a suppression beam, where suppression is minimal, so the signal from the target is not suppressed relative to signal from background molecules. Point scanning is not needed, as a pixelated detector of a camera can be used to acquire the position of the target in one shot. Images of the object from the pixelated detector can be analyzed to acquire the position of the target. To maintain the target in the zero, the beams may be steered onto the target. Alternatively or additionally, the sample may be moved to place the sample in the center. A correction signal may be sent to cause the sample and/or beams to be moved to maintain the target in position.

Abstract: The presently disclosed subject matter provides compositions and methods for in vivo diagnosis and treatment of diseases or disorders associated with DLL3. In particular, the presently disclosed subject matter provides novel anti-DLL3 antibodies-TCO conjugates, which can form a radioimmunoconjugate with a radioligand comprising a radioactive isotope.

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

Abstract: Aspects of the disclosure provide methods for inhibiting cell proliferation and protein synthesis utilizing an antagonist of nicotinamide adenine dinucleotide kinase 2 (NADK2). In some aspects, these methods are used to treat a disease such as cancer or a disorder such as a fibrotic disorder. Further provided herein are compositions comprising a nutrient-deficient cell culture medium and an antagonist of NADK2.

Abstract: The present invention relates to compositions, methods, and kits for predicting a subject's response to a CAR T cell therapy, by analyzing the intestinal microbiome of the subject. The present disclosure also provides a method of detecting patients at risk for a poor response to CAR T cell therapy by measuring the level of the presently disclosed bacteria or bacterial genes in the microflora or microbiome of a patient receiving or considered for CAR T cell therapy. The present disclosure further provides therapeutic compositions and methods for treating a subject having a cancer, by improving the subject's response to a CAR T cell therapy.

Abstract: The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., multiple myeloma). It relates to anti-CD56 antibodies, chimeric antigen receptors (CARs) that specifically target human CD56, and immunoresponsive cells comprising such CARs. The presently disclosed CD56-specific CARs have enhanced immune-activating properties, including anti-tumor activity.

Abstract: The presently disclosed subject matter provides for antigen-recognizing receptors that specifically target CD33 and cells comprising such CD33-targeted antigen-recognizing receptors. The presently disclosed subject matter further provides uses of the CD33-targeted antigen-recognizing receptors for treatment.

Abstract: The presently disclosed subject matter provides for chimeric receptors that target MUC16 and cells comprising such chimeric receptors. The presently disclosed subject matter further provides uses of the chimeric receptors for treatment.

Abstract: Provided are antibodies that specifically bind to CTLA-4 and/or PD-1 and antagonize CTLA-4 and/or PD-1 function. Also provided are pharmaceutical compositions and kits 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 either alone or in combination.

Abstract: The presently disclosed subject matter provides methods and compositions for enhancing the immune response toward cancers and pathogens. It relates to novel designs of chimeric antigen receptors (CARs) and engineered immunoresponsive cells comprising the same. The engineered immunoresponsive cells comprising the novel CARs are antigen-directed and have extended persistence without compromising function.