Abstract: The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

Abstract: The present disclosure provides compositions and methods for treating diseases associated with expression of CD19 and/or CD22, e.g., by administering a recombinant T cell or natural killer (NK) cell comprising a CD22 CAR and a CD19 CAR as described herein. The disclosure also relates to CAR molecules specific to CD22 and/or CD19, methods of making a cell comprising the same and vectors encoding the same.

Abstract: Provided herein are methods and compositions to augment the efficacy and reduce toxicity of non-engrafting, CD8-depeleted allogeneic donor lymphocyte infusions. The compositions comprise isolated leukocytes obtained from a donor subject that (i) are mismatched to a recipient subject for at least one human leukocyte antigen (HLA) Class II allele mismatch in the donor versus recipient (graft-versus-host) direction relative to the recipient subject or (ii) is mismatched to a recipient subject for at least one human leukocyte antigen (HLA) Class II allele mismatch in the donor versus recipient (graft-versus-host) direction relative to the recipient subject, is matched to the recipient for at least one human leukocyte antigen (HLA) Class II allele, and has CD4+ T cell immunity against an antigen present in a recipient subject.

Abstract: The present disclosure provides methods and compositions related to the modification of immune effector cells to increase therapeutic efficacy. In some embodiments, immune effector cells modified to reduce expression of one or more endogenous target genes, or to reduce one or more functions of an endogenous protein to enhance effector functions of the immune cells are provided. In some embodiments, immune effector cells further modified by introduction of transgenes conferring antigen specificity, such as exogenous T cell receptors (TCRs) or chimeric antigen receptors (CARs) are provided. Methods of treating a cell proliferative disorder, such as a cancer, using the modified immune effector cells described herein are also provided.

Abstract: Genetically engineered hematopoietic cells, which express one or more factors that redirect glucose metabolites, and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide, a chimeric antigen receptor (CAR) polypeptide, or a TCR polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered hematopoietic cells for inhibiting cells expressing a target antigen in a subject in need thereof.

Abstract: The disclosure provides single-chain and multi-chain synthetic antigen receptors, methods of making such synthetic antigen receptors and uses thereof for the treatment of diseases and disorder.

Abstract: The present disclosure generally relates to, inter alia, recombinant cells capable of expressing polypeptides, e.g., chimeric antigen receptors (CARs) that can be used for logic gating (e.g., NOT-gating) to specifically target and eliminate some types of cells (e.g., cancer cells). The disclosure also provides compositions and methods useful for producing such recombinant cells or polypeptides, as well as methods for the detection and treatment of diseases, such as cancer.

Abstract: The subject matter described herein is directed to articles, compositions, systems, and methods of using and preparing bioceramic compositions and to the bioceramic compositions. A bioceramic composition of the disclosure radiates infrared energy or rays and can be used in the treatment of various conditions.

Abstract: The invention provides endoplasmic reticulum-targeted chemiluminescent agents and their use in methods of photodynamic therapy (PDT). In particular, the invention provides compounds of general formula (I), and their pharmaceutically acceptable salts: in which A represents a chemiluminescent moiety; each L, which may be the same or different, is either a direct bond or a linker; each B, which may be the same or different, represents an endoplasmic reticulum-targeting moiety; n is an integer from 1 to 3, preferably 1; and x is an integer from 1 to 3, preferably 1. Such compounds find particular use in the treatment of deeply-sited tumours, e.g. glioblastoma multiforme (GBM), when used in combination with a photosensitizer or photosensitizer precursor.

Abstract: A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof, an insulin or/and a pharmacologically tolerable salt thereof, and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin where appropriate.

Abstract: A colon-targeted active agent delivery carrier includes a low methoxyl pectin derived from Jelly fig (Jelly fig LM pectin) and a divalent cation, wherein the Jelly fig LM pectin crosslinks with the divalent cation in an egg-box conformation, wherein the colon-targeted composition is degraded by at least one enzyme in the colon of the subject to release the active agent.

Abstract: The invention relates to a bioactive lipid (BAL) composition comprising one or more hydrocarbon-derivatized fatty acids (FAs), which can be an oxygenated, halogenated, amino, amide, nitro, cyano, furanoid, nitroso, isonitrile, or O-substituted derivative of the hydrocarbon-derivatized FA, which are bound to a molecular backbone. In some embodiments, the BALs comprise a specialized pro-resolving mediator (SPMs), eicosanoid, prostanoid, prostaglandin, or endocannabinoid (eCBs) and optionally further comprise omega-3 (n-3) FAs and/or omega-6 (n-6) FAs. In general, the BALs are conjugated to a molecular backbone, preferably a five- or six-carbon monosaccharide, or glycerol. The compositions can be formulated as an emulsion. Preferred BALs can be selected by their performance in one or more cellular assays or animal models. These compositions are useful for tissue or organ protection in a patient, for example in stroke, ischemia, traumatic injury, a neurodegenerative disorder, or organ injury and/or transplant.

Abstract: The present invention relates to a composition comprising a self-assembled nanocomplex, wherein the self-assembled nanocomplex comprises one or more active agent physically bound to one or more conjugate, wherein each conjugate comprises one or more flavonoid molecule and a first water-soluble polymer, and the nanocomplex is at least partially encapsulated by a second water-soluble polymer. The present invention also relates to a method of preparing the composition and uses thereof. The present invention also relates to a method of treating an eye disease caused by angiogenesis, comprising administering a composition to a subject in need thereof, wherein the composition comprises a self-assembled nanocomplex, wherein the self-assembled nanocomplex comprises an ophthalmic anti-angiogenesis drug physically bound to one or more conjugate, each conjugate comprising one or more flavonoid molecule and a first water-soluble polymer.

Abstract: The present invention provides compounds suitable for use in the treatment of conditions where it is beneficial to halt bone loss and kill cancer cells, particularly in metastases to and primary tumors in the bone and surrounding tissues. Consequently the present invention provides compounds comprising a bisphosphonate moiety linked to a phytochemical, pharmaceutical compositions thereof and methods of treatment of bone diseases and/or proliferative disorders.

Abstract: Chimeric antigen receptor (CAR) T-cell-rejuvenating conjugates and compositions and methods of use to rejuvenate exhausted CAR T-cells.

Abstract: Provided herein are immunoconjugate molecules containing a TNF-? polypeptide and a masking moiety capable of inhibiting and activating the TNF-? activity under suitable conditions. Also provided herein are methods for producing the immunoconjugate molecules. Finally, provided herein are the therapeutic uses of the immunoconjugate molecules due to their modulating effects on the immune system for treating diseases such as cancer and other chronic infectious diseases.

Abstract: The invention provides compositions and methods for the treatment or prevention of pain. Compositions provided are resistant to overdose and abuse. Compositions provided comprise two or more different molecules, where each molecule comprises at least one GI enzyme-labile opioid agonist releasing subunit comprising an opioid agonist that is covalently linked to at least one GI enzyme inhibitor subunit.

Abstract: The present invention aims to provide a novel drug delivery system (DDS) technique capable of selectively delivering a drug (compound containing oligonucleotides for producing at least partially functional dystrophin protein) to muscle tissues such as cardiac muscle, skeletal muscle and the like and efficiently introducing the drug into the muscle cells. The present invention relates to a conjugate or a salt thereof including the following: (1) a peptide that binds to a transferrin receptor, and contains the amino acid sequence shown in SEQ ID NO: 1 (Ala-Val-Phe-Val-Trp-Asn-Tyr-Tyr-Ile-Ile-Ser-Cys); or an amino acid sequence resulting from substitution, deletion, addition, and/or insertion of not less than one and not more than 10 amino acid residues in the amino acid sequence shown in SEQ ID NO: 1, and (2) a compound comprising an oligonucleotide for producing an at least partially functional dystrophin protein.

Abstract: Provided are an antibody-drug conjugate, a preparation method therefor, and a pharmaceutical use thereof, and specifically related are an anti-TROP-2 antibody-drug conjugate and a pharmaceutical use thereof. The antibody-drug conjugate is formed by connecting an anti-TROP-2 antibody or an antigen binding fragment thereof and an exitecan derivative by means of a linker, and the antibody-drug conjugate or a pharmaceutically acceptable salt or solvent compound thereof has a significant anti-tumor effect and good safety.

Abstract: Provided herein are protein complexes comprising a sensor domain and a therapeutic domain linked by a linker, and methods of use thereof. In aspects of the present disclosure, activity of the therapeutic domain comprises a dependence on sensor domain binding to target markers.

Abstract: Described herein are methods for inhibiting a solid tumor expressing claudin-6 in a human subject, comprising administering to the human subject an effective amount of a composition comprising conjugates of a CLDN6-specific antigen-binding protein covalently bound to heterologous moieties comprising structural formula (I): wherein a first plurality of the conjugates are bound to four heterologous moieties comprising structural formula (I); at least about 95% of the first plurality of conjugates are structurally homogenous; and the effective amount is in a range of about 1.0 mg of conjugate/kg weight of the subject to 10 mg of conjugate/kg weight of the subject.

Abstract: The present disclosure relates to the field of therapeutic methods for treating a cancer using an ADC. The present disclosure also relates to the field of pharmaceutical products comprising the ADC for treating a cancer. More specifically, the ADC is composed of an anti-cadherin-6 (CDH6) antibody connected via a linker to an anticancer agent, such as topoisomerase I inhibitor, and the cancer may be resistant to chemotherapy.

Abstract: A composition is useful for treating inflammatory diseases, in which hydrophobic manganese oxide is loaded on micelles so as to be stably protected in vivo thereby easily being delivered to a target site. In addition, the hydrophilic and hydrophobic regions of micelles are bonded with a reactive oxygen species (ROS) cleavable linker and decomposed in response to active oxygen species at an inflammatory site, thereby efficiently releasing hydrophobic manganese oxide particles, and released hydrophobic manganese oxide can generate oxygen to change the microenvironment of the target site, thereby improving the effects of physiologically active substances loaded on the micelles.

Abstract: The disclosure relates generally to polyglutamated antifolates, formulations containing liposomes filled with the polyglutamated antifolates, methods of making the polyglutamated antifolates and liposome containing formulations, and methods of using the polyglutamated antifolates and liposome containing formulations to treat hyerproliferative disorders (e.g., cancer) and disorders of the immune system (e.g., an autoimmune disease such as rheumatoid arthritis).

Abstract: The present invention relates to aqueous cyclodextrin compositions containing drug/cyclodextrin complexes and sorbic acid or a pharmaceutically acceptable sorbate that exhibit a superior antimicrobial preservation effect at a low preservative concentration, and to an aqueous eye drop microsuspension containing solid drug/cyclodextrin complexes and sorbic acid or a pharmaceutically acceptable sorbate, which is suitable as a multidose formulation.

Abstract: Provided are recombinant adeno-associated virus (r.AAV) vectors comprising a transgene to express galactose-1-phosphate uridylyl transferase (GALT); virions comprising said vectors (r.AAV virions); methods of their production; methods of their use, including methods for treating galactosemia, GALT-deficiency, symptoms therefrom: and kits. These recombinant adeno-associated virus (rAAV) vectors comprise a method of treating galactosemia in a subject in need.

Abstract: The present disclosure provides variant AAV8 capsids that exhibit altered capsid properties, e.g., improved transduction efficiency and/or specificity for the liver. The present disclosure further provides nucleic acids encoding the variant AAV8 capsids, recombinant AAV (rAAV) vectors comprising the variant AAV8 capsids, as well as host cells and compositions comprising the same. The present disclosure further provides methods of delivering a gene product to a subject and methods of treatment of a liver-borne blood disorder, the methods generally involving administering an effective amount of the rAAV vectors to a subject in need thereof.

Abstract: Aspects of the disclosure relate to compositions and methods for epigenetic regulation of endogenous gene expression from viral vectors. In some embodiments, the disclosure provides expression constructs comprising a viral vector encoding a transgene, the activation of which is regulated by a rapamycin/rapalog-based system, and the transgene is capable of epigenetically regulate an endogenous gene.

Abstract: Provided herein is a gene therapy for PKP2 (Plakophilin-2), e.g. using an adeno-associated virus (AAV) vector. The promoter of the vector may be a MHCK7 promoter or a cardiac troponin T (HTNNT2) promoter. The capsid may be an AAV9 or AAVrh74 capsid or a functional variant thereof. Other promoters or capsids may be used. Further provided are methods of treatment, such as by intravenous, intracoronary, intracarotid or intracardiac administration of the rAAV vector, and other compositions and methods.

Abstract: Disclosed herein are novel gene editing systems capable of being delivered to a subject intravenously through a lipid nano particle pharmaceutical formulation and producing durable in vivo editing of a target gene, such as ANGPTL3, with high on-target gene editing efficiency, reduced or low off-target effect, and no germline editing. The gene editing systems comprise a chemically modified guide nucleic acid sequence with a spacer having a specified arrangement of deoxyribonucleotides and ribonucleotides. The novel gene editing systems comprise mRNA that encodes the gene editor proteins, which may include a modified nickase component. Methods of disease treatments using the gene editing systems are also disclosed.

Abstract: The present disclosure provides AAV vectors encoding a modified chimeric ligand gated ion channel and methods for the treatment of trigeminal neuralgia in a subject in need thereof.

Abstract: The disclosure provides compositions and methods for producing micro-dystrophin proteins, and the use thereof (e.g., in gene therapy). The disclosure also provides skeletal muscle-specific promoters and the use thereof (e.g., in gene therapy). The disclosure further provides catheter-based methods of delivering gene therapy vectors to skeletal muscle and/or cardiac muscle.

Abstract: Provided herein are compositions for gene modification or editing and methods of using same to treat or prevent certain conditions. Specific compositions and methods capable of safely and effectively editing gene targets expressed in the liver to durably lower LDL-C thereby treating a leading cause of cardiovascular disease are disclosed.

Abstract: Disclosed herein are RNA polynucleotides comprising a 5? Cap, a 5? UTR comprising a cap proximal sequence disclosed herein, and a sequence encoding a payload. Also disclosed herein are compositions and medical preparations comprising the same, and methods of making and using the same.

Abstract: Disclosed herein is a device for producing NIR-II contrast agents from fluorescent substances and serum albumin. The device comprises a first container, a mixing vessel, a first tube, and a first flow adjusting valve. According to the embodiments of the present disclosure, the first container and the mixing vessel are connected through the first tube, and the first flow adjusting valve is coupled to the first tube. Also disclosed herein are methods for producing the NIR-II contrast agents by using the present device.

Abstract: Near-infrared fluorescent dye-loaded microspheres and a formulation thereof that include a complex of a near-infrared fluorescent dye and human serum albumin or cyclodextrin loaded into polymer microspheres, optionally with a hydrogel polymer. The near-infrared fluorescent dye-loaded microspheres are used in a method of marking lesions for accurately identifying the location of lesion sites from fluorescence imaging during surgery. The method involves injecting the microspheres into lesion sites in a subject, such as cancer. The intensity of fluorescence generated from the microspheres is stronger than that when microspheres are prepared using a near-infrared fluorescent dye alone, the stability of the fluorescent dye in the microspheres is improved, and the marked sites can be identified through fluorescent imaging for a long period of time, increasing the accuracy of surgery for lesion excision, and shortening the time required for surgery.

Abstract: In some aspects the present disclosure provides a radiopaque, reactive copolymer comprising at least one hydrophilic polymer segment having a plurality of hydrophilic polymer segment ends, a plurality of iodinated polymer segments covalently linked to the plurality of hydrophilic polymer segment ends, and a plurality of reactive moieties covalently linked to the iodinated polymer segments. In other aspects, the present disclosure pertains to a system for forming a hydrogel composition that comprises (a) such a radiopaque, reactive copolymer and (b) a nucleophilic compound, as well as to a crosslinked reaction product of the same. In further aspects, the present disclosure pertains to a method of treatment comprising administering to a subject a mixture that comprises (a) such a radiopaque, reactive copolymer and (b) a nucleophilic compound, under conditions such that the nucleophilic compound and the radiopaque, reactive copolymer crosslink after administration.

Abstract: Nanostructures that, after in vivo administration, are excreted in the urine via the kidneys without being phagocytosed by macrophages and/or metabolized, and their use as pharmaceutical compositions are disclosed. A nanostructure for in vivo administration contains (i) a spherical core formed by crosslinking one to three dextran molecules with an average molecular weight of 10,000 Da or less using a crosslinker and (ii) a discontinuous shell with divalent or trivalent iron ions coordinationally bonded to crosslinker-derived hydrophilic groups on the surface of the spherical core; and has (iii) a mass ratio of dextran to iron ranging from 100:2 to 100:10, and a charge ranging from ?20 mV to 0 mV.

Abstract: The present invention relates to a dual-mode probe for detecting of hydrogen sulfide and use thereof and, more specifically to a dual-mode probe that has excellent blood-brain barrier permeability and is capable of fluorescence and nuclear imaging and a use thereof for detecting hydrogen sulfide.

Abstract: Compounds of Formula (I) and Formula (II), which are capable of binding to granzyme B. Also provided herein are pharmaceutical compositions comprising such for use in, for example, imaging Granzyme B and/or treating immunoregulatory abnormalities.

Abstract: Aspects of the present disclosure relate generally to novel antigen binding sequences and uses thereof. More specifically, certain features of the present disclosure concern antibodies, minibodies, and cys-diabodies for use in targeting the protein FAP. The antigen binding sequences herein may be used as part of treatment to confer health benefits to subjects in need thereof. The antigen binding sequences can also be used for detection, targeting, and imaging purposes.

Abstract: Methods for treating cancers and precancerous conditions by administering an effective amount of a radiolabeled agent that targets cell surface GRP78, alone or in combination with other therapies, are provided. The radiolabeled GRP78 targeting agent delivers radiation to cells that externally present GRP78, such as tumor cells, depleting those cells and neighboring malignant cells to effect overall tumor reduction. Radiation delivered by the radiolabeled GRP78 targeting agent itself increases the cell surface expression of GRP78, leading to a feed-forward mechanism that drives further accumulation of the GRP78 targeting agent at target lesions to enhance its therapeutic effect.

Abstract: A disinfecting light apparatus configurable through the use of switchable mirror panels, occupancy sensors, and reflective louvers is disclosed. The disinfecting light apparatus controls the emission of disinfecting light using switchable mirror panels. The occupancy sensors generate occupancy signals used to determine the dimming level of the switchable mirror panels. The reflective louvers are configured to direct disinfecting light 5horizontally to disinfect the “upper-air.” The switchable mirror panels, occupancy sensors, and reflective louvers allow for the disinfecting light apparatus to switch between different modes. For example, if the occupancy sensors do not detect any persons in their fields of view, the disinfecting light apparatus operates in a “Surface Disinfection” mode. If the occupancy sensors detect a person, the disinfecting light apparatus operates in “Upper-Air 10Disinfection” mode.

Abstract: A sterilization and deodorization waste container includes an isolation chamber provided on an inner side of a container lid and a dual-band ultraviolet lamp tube installed in the isolation chamber. The dual-band ultraviolet lamp tube is capable of simultaneously generating a direct ultraviolet light wave and an ozone ultraviolet light wave. The isolation chamber includes a reflector housing having a light transmitting window facing an inner cavity of a container body. The dual-band ultraviolet lamp tube is controlled by a control circuit to turn on to generate the ultraviolet light rays into an inner cavity of the container body while the container lid is closed and to turn off to stop generating the ultraviolet while the container lid is opened.

Abstract: An object of the present invention is to provide an ultraviolet light irradiation sheet that can be decontaminated regardless of a shape of an object to be decontaminated. An ultraviolet light irradiation sheet (50) includes an optical fiber (20) which emits a part of propagating light from a side surface or an end surface; and a deformable sheet (10) which incorporates the optical fiber (20). The ultraviolet light irradiation sheet uniformly or partially irradiates ultraviolet light from a sheet surface. Therefore, by covering the object to be sterilized with the ultraviolet light irradiation sheet, a material having a complicated shape or an amorphous shape can be irradiated with the ultraviolet light without making a shade. Since the ultraviolet light irradiation sheet does not diffuse bacteria and viruses by wind, the sterilization of the object to be sterilized can be performed without forming a closed space.

Abstract: A system for centrally controlled sanitization of a lavatory of an aircraft using ultraviolet (UV) light includes a first UV light source configured to emit a first UV light, and a second UV light source configured to emit a second UV light. The system further includes a central controller coupled to the first UV light source and the second UV light source and configured to independently control the first UV light source and the second UV light source to emit the first UV light and the second UV light at least one of at different times or for different durations.

Abstract: A sanitizing device particularly suitable for sanitizing personal use items such as a menstrual cup and other smaller size personal items having varying shapes that are capable of fitting within a tapered dome or cone like shaped housing. The sanitizing device includes top and bottom half members, top and bottom reflective members positioned within the top and bottom half members, respectively, and a planar quartz glass member to ensure that all interior and exterior surfaces of the menstrual cup or other smaller size personal items are adequately exposed to UVC light to achieve sanitization.

Abstract: An apparatus for sanitizing a point-of-contact surface may include a housing configured to be affixed about at least a portion of said point of contact. The housing may have an interior in or through which the point of contact may be accessed and an anterior opening for access to the interior. The apparatus may further include one or more sources of a sanitizing agent, such as germicidal light, configured to direct the sanitizing agent toward a location where at least a portion of the point-of-contact surface may be disposed. One or more of an anterior dome, an inner surface, and a posterior surface may also be configured to reflect the sanitizing agent toward the location where at least a portion of the point-of-contact surface may be disposed.

Abstract: A water disinfection apparatus includes an air pump, a chamber including a rod, a turbine connected to a water supply and configured to translate energy from the water supply to rotate the air pump and the rod, an ozone supply downstream of the air pump and connected to the chamber, and a water path from the turbine to the chamber.

Abstract: An orthopaedic surgical instrument system includes a sterilization tray for storage of orthopaedic surgical instruments during sterilization and transport thereof. The sterilization tray has a masking layer disposed on the upper surface of its bottom wall.