Abstract: Some aspect of this disclosure provide reversible MHC protein multimers, and methods of using such multimers in the detection and/or isolation of specific T-cells or T-cell populations. Because reversible MHC multimers can efficiently be dissociated, the time of MHC binding to T-cell receptors, and, thus, T-cell receptor-mediated T-cell activation can be minimized. The use of reversible MHC multimers as provided herein, accordingly, allows for the detection and isolation of bona fide antigen-specific CD8+ T cells without inducing activation dependent cell death, including rare, therapeutically valuable T-cells expressing T-cell receptors binding tumor antigens with high affinity. Methods for the production and use of reversible multimers are also provided.

Abstract: Chimpanzee adenovirus (ChAd) and MVA virus vectors containing polynucleotide sequences encoding cancer antigens are administered sequentially to a subject in a suitable adjuvant in order to achieve a prime boost effect. The polynucleotides are expressed in situ following administration to provide a MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. Also, a hli/MAGEA3/linker/NY-ESO-1 fusion protein and variants thereof. An improved T cell response is found. In a particular synergistic therapeutic approach a triple combination of ChAdOx and MVA vectors together with chemotherapeutic agent and checkpoint inhibitor results in depleted myeloid derived suppressor cells (MDSC) and dramatically improves survival time in a mouse model of cancer.

Abstract: The present invention relates to methods for haplotype determination and, in particular, haplotype determination at the whole genome level as well as targeted haplotype determination.

Abstract: The invention relates to a double-stranded ribonucleic acid (dsRNA) targeting a mutant Epidermal Growth Factor Receptor (EGFR), and methods of using the dsRNA to inhibit expression of mutant EGFR.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for increasing the amount or activity of STMN2 RNA in a cell or animal, and in certain embodiments increasing the amount of STMN2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include ataxia, neuropathy, synaptic dysfunction, deficits in cognition, and decreased longevity. Such neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).

Abstract: The present invention relates to a population of lymphocytes comprising at least 90% CD3+ T cells and less than 5% B cells, wherein at least 70% of said T cell portion are viable, at least 20% are CD27/CD28 double positive and less than 10% are triple positive for CD45RA, CD57 and KLRG1 and a method for expansion of a population of lymphocytes specific for one or more antigens comprising a single culture phase.

Abstract: This disclosure provides methods for bisulfite-free identification in a nucleic acid sequence of the locations of 5-methylcytosine, 5-hydroxymethylcytosine, 5-carboxylcytosine and 5-formylcytosine.

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: This disclosure provides methods for bisulfite-free identification in a nucleic acid sequence of the locations of 5-methylcytosine, 5-hydroxymethylcytosine, 5-carboxylcytosine and 5-formylcytosine.

Abstract: This disclosure provides methods for bisulfite-free identification in a nucleic acid sequence of the locations of 5-methylcytosine, 5-hydroxymethylcytosine, 5-carboxylcytosine and 5-formylcytosine.

Abstract: Specific binding members, particularly antibodies and fragments thereof, which bind to transforming growth factor beta 1 (TGF-?1) are provided, particularly recognizing human and mouse TGF-?1 and not recognizing or binding TGF-?2 or TGF-?3. Particular antibodies are provided which specifically recognize and neutralize TGF-?1. These antibodies are useful in the diagnosis and treatment of conditions associated with activated or elevated TGF-?1, including cancer, and for modulating immune cells and immune response, including immune response to cancer or cancer antigens. The anti-TGF-?1 antibodies, variable regions or CDR domain sequences thereof, and fragments thereof may also be used in therapy in combination with chemotherapeutics, immune modulators, or anti-cancer agents and/or with other antibodies or fragments thereof. Antibodies of this type are exemplified by the novel antibodies hereof, including antibody 13A1, whose sequences are provided herein.

Abstract: The present disclosure provides methods for selectively tagging 5-methylcytosine in a DNA sample and using this approach for genome-wide profiling of 5-methylcytosine in a low input DNA sample such as circulating cell-free DNA.

Abstract: The present disclosure provides antibodies that specifically bind to human glucocorticoid-induced TNFR family related receptor (GITR) and compositions comprising such antibodies. In a specific aspect, the antibodies specifically bind to human GITR and modulate GITR activity, e.g., enhance, activate or induce GITR activity, utilizing such antibodies. The present disclosure also provides methods for treating disorders, such as cancer and infectious diseases, by administering an antibody that specifically binds to human GITR and modulates GITR activity e.g., enhances, activates or induces GITR activity.

Abstract: The present disclosure relates to novel PD-1 decoy variants, compositions, and methods to confer and/or increase immune responses mediated by cellular immunotherapy, such as by adoptively transferring tumor-specific genetically-modified subsets of lymphocytes.

Abstract: Provided are compounds, methods, and pharmaceutical compositions for increasing the amount or activity of STMN2 RNA in a cell or animal, and in certain embodiments increasing the amount of STMN2 protein in a cell or animal. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom of a neurodegenerative disease. Such symptoms include ataxia, neuropathy, synaptic dysfunction, deficits in cognition, and decreased longevity. Such neurodegenerative diseases include amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and dementia with Lewy bodies (DLB).

Abstract: A method for characterising motion of one or more objects in a time ordered image dataset comprising a plurality of time ordered data frames, the method comprising: selecting a reference data frame from the plurality of time ordered data frames (210); extracting a plurality of image patches from at least a part of the reference data frame (220); identifying a location of each image patch of at least a subset of the plurality of image patches in each data frame (230); defining, based on the identified locations, a mesh for each data frame, wherein vertices of each mesh correspond to respective identified locations of image patches in the corresponding data frame (240); and deriving, from the meshes, a motion signature for the time ordered image dataset, the motion signature characteristic of the motion of the one or more objects in the plurality of time ordered data frames (250).

Abstract: The present invention relates to methods of designing kinase mutants for reprogramming the sensitivity of a target kinase to some specific inhibitors, methods of reprogramming the sensitivity of a target kinase to some specific inhibitors, wherein those kinase inhibitors have little or no affinity for the wild-type target kinase, vectors or cells expressing said mutated kinases, composition and uses thereof for the prevention and/or treatment of a disease or disorder, in particular cancer.

Abstract: The present invention relates to methods for the joint analysis of regulation of gene expression and gene expression in single cells. Provided are methods for obtaining gene expression information for a single nucleus, the methods comprising deriving a DNA library from the genomic DNA in one or more nuclei and deriving an RNA library from the RNA in one or more nuclei, sequencing the molecules in the RNA library and the DNA library, and correlating the RNA library and the DNA library for each of the one or more nuclei.

Abstract: The invention relates to chimeric antigen receptors (CARs) targeting a cancer-associated antigen and their use for treatment of a tumor or cancer. In particular, the invention provides compositions and methods for treating diseases associated with the antigen NGcGM3. The invention also relates to CARs specific to NGcGM3, vectors encoding the same, and recombinant T cells comprising the CARs of the present invention. The invention also includes methods of administering a genetically modified T cell expressing a CAR that comprises an antigen binding domain that binds to NGcGM3.

Abstract: The instant disclosure provides antibodies that specifically bind to CTLA-4 (e.g., 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.