Abstract: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.

Abstract: The present application relates to compositions comprising fusion proteins and cells expressing the proteins. The application further relates to methods of using the fusion proteins, cells, and compositions for modulating cell signaling and for selective expansion of cells.

Abstract: Disclosed are methods of making a genetically cell that expressed FOXP3 and methods of treatment. In some embodiments, the method can providing a first nucleotide sequence, wherein the first nucleotide sequence comprises a coding strand, the coding strand comprising one or more regulatory elements and a FOXP3 gene or portion thereof providing a nuclease and performing a gene editing process on the first nucleotide sequence, which edits said one or more regulatory elements, and optionally edits the FOXP3 gene or portion thereof. Methods of treating a subject suffering from an autoimmune disease and subjects suffering the effects of organ transplantation are also provided.

Abstract: Aspects of the invention described herein concern the incorporation of a FOXP3 cDNA (e.g., full-length human codon-optimized cDNA) into a FOXP3 gene or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human CD34+ cells or cells derived from edited CD34+ cells. In some embodiments, guide RNA sequences that are directed to FOXP3, AAVS1, or other candidate loci are used for CRISPR/Cas9-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided.

Abstract: Systems, apparatuses, and methods enable rapid, repeatable, and accurate dissection of arthropods. Arthropod dissection apparatuses includes a shear dissection mechanism having a primary shear body and a secondary shear body. The primary shear body includes at least an inlet channel, a first outlet channel, and a second outlet channel formed therein. The secondary shear body is disposed in an aperture of the primary shear body and has a dissection chamber formed therein. The secondary shear body is movable between a first position and a second position relative to the primary shear body, which causes a shearing action at a shearing interface between the secondary shear body and the primary shear body.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: The current disclosure provides antibodies that bind to peptides associated with the primary immunodeficiency disorders (PIDD) Wiskott-Aldrich Syndrome (WAS) and X-linked agammaglobulinemia (XLA). The antibodies can be used in peptide immunoaffinity enrichment coupled to selected reaction monitoring mass spectrometry (immuno-SRM) assays for clinical diagnosis and newborn screening of WAS and XLA, among other uses.

Abstract: Aspects of the invention described herein relate to synthetic compounds that are useful for targeting and labeling tumor cells so as to facilitate recognition by binding agents including Chimeric Antigen Receptor T cells (CAR T cells), which are administered to a subject by intravenous or locoregional administration. Several compositions and methods of making and using these compositions to treat or inhibit a disease in a subject are contemplated.

Abstract: Described herein are systems and methods for treating, inhibiting, or ameliorating X-linked disorders including Wiskott-Aldrich Syndrome (WAS) and X-linked thrombocytopenia (XLT) in subjects that have been identified or selected as being ones that would benefit from a therapy to treat, inhibit, or ameliorate WAS or XLT. The systems include nuclease and vector donor constructs configured for co-delivery to modify endogenous WAS locus.

Abstract: The invention is directed to a bispecific chimeric antigen receptor, comprising: (a) at least two antigen-specific targeting regions; (b) an extracellular spacer domain; (c) a transmembrane domain; (d) at least one co-stimulatory domain; and (e) an intracellular signaling domain, wherein each antigen-specific targeting region comprises an antigen-specific single chain Fv (scFv) fragment, and binds a different antigen, and wherein the bispecific chimeric antigen receptor is co-expressed with a therapeutic control. The invention also provides methods and uses of the bispecific chimeric antigen receptors.

Abstract: Systems and methods for promoting neuroplasticity in a brain of a subject to improve and/or restore neural function are disclosed herein. One such method includes detecting residual movement and/or muscular activity in a limb of the subject, such as a paretic limb. The method further includes generating a stimulation pattern based on the detected movement and/or muscular activity, and stimulating the brain of the subject with the stimulation pattern. It is expected that delivering stimulation based on the detected residual movement and/or muscular activity of the limb will induce neuroplasticity for restoring neural function, such as control of the limb. A second method involves detecting brain signals and delivering contingent stimulation. A third method involves delivering pairs of successive stimulus patterns to two brain sites, controlled either by preprogrammed sequences or contingent on neural or muscular activity or movement.

Abstract: Photosensitizers are incorporated into articles, such a personal protective equipment. A method of applying continuous and consistent light includes fitting the articles with light sources and optical fibers to apply light to the areas of the articles incorporated with the photosensitizers. Photosensitizers can be applied to articles by various applicators in either a gel or solution. A gel can be particularly effective when used on hydrophobic surfaces. Photodynamic reactor systems can be used to determine the effective doses of photosensitizers and the light dosimetry which can then be applied for use with the articles.

Abstract: The invention provides a gene signature for use in determining a likelihood of a latent tuberculosis (TB) infection in a subject transitioning to active TB disease. The gene signature comprises at least SEPT4 and BLK, and optionally also GAS6 and/or CD1C. Expression levels of these genes are detected in a sample from the subject, and the ratios of expression of at least two of the above genes are calculated (e.g. SEPT4:BLK, SEPT4:CD1C, GAS6:BLK and/or GAS6:CD1C). A score is assigned to each ratio, the score being indicative of the likelihood of the latent TB infection transitioning into active TB disease, based on the ratio for the respective gene pair. The subject can be identified as having a latent TB infection that is likely to transition into active TB disease or that is not likely to transition into active TB disease based on the score or on the average of the scores.

Abstract: Described herein are aptamers that bind to the transferrin receptor (e.g., CD71) and can be used, in part, for depleting transferrin receptor-expressing cells from a population of therapeutic cells. These aptamer compositions can be used in methods for isolating and/or enriching cells expressing CD71 or depleting cell populations of cells expressing CD71, including for example, tumor cells. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Abstract: The present disclosure provides a method of detecting the presence of a hypnozoite stage of Plasmodium vivax in a liver cell. In addition, the present disclosure provides compositions and methods of detecting the presence of a latent Plasmodium vivax infection in a subject and for treating the subject detected to be infected.

Abstract: Provided herein are compositions comprising aptamers that specifically bind monocytes and/or macrophage and methods for their use. These aptamer compositions can be used in methods for isolating and/or enriching monocytes and/or macrophages or depleting cell populations of monocytes and/or macrophages. Further provided are methods of using the aptamers or cell populations generated using them in the methods disclosed herein for therapies and/or drug delivery.

Abstract: The invention provides compositions and methods for preventing or reducing the severity of malaria.

Abstract: An apparatus for vaccine generation includes a syringe with a cavity that includes a solution with photosensitizers. Microbial particles are added to the solution. A light source is capable of emitting one or more wavebands of light that are effectively absorbed by the one photosensitizers to generate singlet oxygen in the solution and other radical species that rapidly react with and damage lipids, proteins, DNA, and RNA of the microbial particles. This damage produces immunogens that can be applied as a vaccine to viruses and other infectious microbial particles. A plunger that fits within a proximal opening in the syringe is used for forcing the solution including the immunogens through the filter and out of the syringe while the photosensitizers, debris and unwanted microbial particles are trapped within the filter.

Abstract: The disclosure relates to doubly attenuated malaria parasites that have had the functionality of LISP2 and PlasMei2 genes interrupted through genetic manipulation. The double attenuated malaria parasites disclosed herein are useful for methods and compositions for stimulating of vertebrate host immune systems because of the complete cessation of lifecycle progression in the late liver stage, while providing a comprehensive antigenic presentation representing wildtype liver stage parasites. The disclosure also relates to the additional blood stage and gametocyte antigens to compositions of genetically attenuated malaria parasites (GAPs) to enhance efficient immune stimulation and prevention of disease and transmission related to the presence of blood stage parasites.

Abstract: Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.