Abstract: The present invention provides methods for making polysaccharide-protein conjugates in which polysaccharides, typically from bacteria, are conjugated to a carrier protein by reductive amination under conditions which improve conjugation reaction consistency, increase consumption of protein during conjugation reaction, generate conjugates of higher molecular weight, and/or reduce the levels of free cyanide in the conjugate reaction product. The polysaccharide-protein conjugates obtained using these methods are useful for inclusion in multivalent vaccines.

Abstract: An enveloped viral particle producer or packaging cell, wherein the cell is genetically engineered to decrease expression of MHC-I on the surface of the cell.

Abstract: The invention provides a recombinant West Nile virus, in which the amino acid sequence of envelope E protein is genetically modified to attenuation, and its RNA genome is inserted with a foreign gene fragment. The engineered E gene contains the mutation of five amino acids for reducing its neural virulence to the central nervous system; the integrated foreign gene between E and S1 gene makes a new chimerical virus. Thus, the present invention provides the application of this attenuated West Nile virus as a vaccine in preventive medicine and the application of the RNA-viral vector as a novel gene-drug in the pharmaceutical industry. The newly attenuated virus may fill the gap of no live-attenuated vaccine to the West Nile virus epidemic. The attenuated and recombinant virus can be used as an RNA oncolytic virus to target solid tumors, especially neural tumors, for cancer therapy with higher safety.

Abstract: The present application belongs to the technical field of gene therapy, and discloses a method for treating a tumor with a combination of an exogenous antigen and a therapeutic agent. The present application also discloses a composition including an exogenous antigen and a therapeutically effective amount of a therapeutic agent. With the exogenous antigen as a target, the therapeutic agent kills a tissue or cell carrying the exogenous antigen and does not act on any tissue or cell without the exogenous antigen, thereby specifically killing the tissue or cell, such as a tumor cell. Since the exogenous antigen can be expressed in different types of tumors in different individuals, the method of the present application is a broad-spectrum anti-tumor method.

Abstract: Disclosed herein are methods for enhancing immune responses to a vaccine in immunocompromised individuals, including those receiving a statin therapy. Related products are also provided.

Abstract: A recombinant virus containing a degron, a preparation method therefor, and an application thereof. At least one viral protein of the recombinant virus containing the degron contains at least one degron capable of being recognized by a protein degradation system of a host cell, wherein the degron comprises any one of or a combination of at least two of an amino acid sequence, a polypeptide, or a structural motif. Further provided are a nucleic acid molecule, a recombinant vector, a preparation method for the recombinant virus containing the degron, a preparation system for the recombinant virus containing the degron, a vaccine, an oncolytic virus, and a drug. The recombinant virus containing the degron can be recognized and degraded by the protein degradation system in the host cell, the replication capability is weakened or even removed, and after a corresponding vaccine, oncolytic virus or drug is prepared, a good effect and practical application value are achieved.

Abstract: The present invention relates to optimized nucleotide sequence encoding SARS-COV-2 antigens. These sequences are particularly suitable for use in vaccine compositions for the treatment or prevention of infections caused by a ?-coronaviruses, including COVID-19 infections, in a human or animal subject in need of such treatment.

Abstract: Described within is a new much improved host-vector systems for delivery of synthesized antigens or of DNA vaccines to a diversity of animal and human hosts to elicit immune responses, especially protective immune responses to control infection and disease induction and/or transmission by bacterial, viral, parasite and fungal infectious disease agents.

Abstract: The present invention discloses a system and method of generating robust immune response in mammals against SARS-CoV-2 antigen by administering two or more doses of same or different COVID-19 vaccines through same or different routes, wherein at least one vaccine is selected from a primary series of vaccines and at least one vaccine is selected from a secondary series of vaccines and wherein vaccines of primary and secondary series are administered through homologous or heterologous routes. The homologous route of administration comprises administering primary and secondary series of vaccines through same route. The heterologous route of administration comprises administering primary and secondary series vaccines through different routes. The system and method of the invention induces superior cross protection against SARS-CoV-2 variants including against Delta and Omicron variants.

Abstract: Disclosed is a pharmaceutical composition to prevent transmission of a pathogen (i.e., including SARS-CoV-2 amongst other pathogens), the pharmaceutical composition comprising: genetically modified bacteria; sequences of small peptides; and pharmaceutical excipients, wherein the genetically modified oral bacteria are modified to translate, produce, and emit the sequences of small peptides which neutralize a pathogen (i.e., including SARS-CoV-2 amongst other pathogens), wherein transgenic technology is used to modify the genetically modified oral bacteria to add genes in genetically modified oral bacteria that are transcribed to produce small peptides from the sequences of small peptides so added, wherein the sequences of small peptides show extreme binding and neutralization to a pathogen (i.e., including SARS-CoV-2 amongst other pathogens) but not to host proteins or processes, and wherein the pharmaceutical excipients aid the oral and/or nasal administration of the pharmaceutical composition.

Abstract: This application relates to a method for increasing tolerance to cashew in a subject. In some examples, the method includes administering to the subject a cashew allergen in combination with at least one regulatory Treg peptide from human immunoglobulin G (IgG) by an epicutaneous route.

Abstract: Methods for the production of immunogenic compositions containing a non-natural amino acid are disclosed. The non-natural amino acid can be a site for attachment of antigens, such as bacterial capsular polysaccharides, to make immunogenic conjugates. Bio-orthogonal attachment chemistry incorporated into the non-natural amino acids allows for more efficient and potent antigen presentation to the immune system, simplified purification, and more well-defined structure of these semi-synthetic immunogens.

Abstract: A composition, method and system are provided for an antibody activator. The composition includes an antigen and iodine. The method for preparing the composition includes providing an antigen, providing an iodine carrier for the antigen, and combining the antigen and the iodine carrier. The system for preparing the composition for antibody activation includes an airless reservoir to contain a volume of iodine, an injection device for injecting an antigen into the reservoir containing the iodine, and a pump for pumping the antigen and iodine mixture from the reservoir to a delivery device.

Abstract: A silicon dioxide vaccine delivery system uses virus-like particles as templates. The particle morphology of the silicon dioxide vaccine system is 50-500 nm of nanoparticles, of which an antigenic component is 20-200 nm of virus-like particles, an adjuvant component is nano silicon dioxide, the silicon dioxide component is wrapped on the surface of the virus-like particle, and a mass ratio of silicon element to antigen is 50-0.5:1. The construction of the silicon dioxide vaccine delivery system includes steps of: (1) adding a proper amount of 3-aminopropyltriethoxysilane into an aqueous solution containing virus-like particles and stirring; (2) adding a proper amount of tetraethoxysilane into the dispersion system in step (1) and stirring; and (3) centrifuging a reactant obtained in step (2) and removing a supernatant to obtain a product. A vaccine constructed by means of the vaccine system can trigger a host to generate humoral and cellular immune levels.

Abstract: The present disclosure provides, among other things, compositions (e.g., autoantibodies) that inhibit the growth, viability, or mobility of (invasion by) a cancer cell. Also provided are applications, such as therapeutic and diagnostic methods, in which the agents are useful, as well as screening methods for identifying autoantibodies useful in the applications.

Abstract: The present invention relates to MASP-3 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-3 dependent complement activation.

Abstract: The present invention provides glycan-interacting antibodies and methods for producing glycan-interacting antibodies useful in the treatment and prevention of human disease, including cancer. Such glycan-interacting antibodies include monoclonal antibodies, derivatives, and fragments thereof as well as compositions and kits comprising them. In some embodiments, the present invention provides an antibody having a heavy chain with an amino acid sequence comprising at least 95% sequence identity to SEQ ID NO: 63 and having a light chain with an amino acid sequence comprising at least 95% sequence identity to SEQ ID NO: 64.

Abstract: The current invention includes compositions and methods comprising immune effector cells modified to express miR-29a for the purpose of resisting immune exhaustion. In various embodiments the transmembrane domain comprises a transmembrane region of a protein selected from the group consisting of a type I transmembrane protein, an alpha chain of a T cell receptor, a beta chain of a T cell receptor, a zeta chain of a T cell receptor, CD28, CD2, CD3 epsilon, CD45, CD4, CD5, CD7, CD8, CD9, CD16, CD22, CD33, CD37, CD64, CD80, CD86, CD134 (OX-40), CD137 (4-1BB), CD154 (CD40L), CD278 (ICOS), CD357 (GITR), Toll-like receptor 1 (TLR1), TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, and TLR9.

Abstract: Provided herein is a cytotoxic immune cell that is primed by and/or whose cytotoxicity within the tumor microenvironment is enhanced by binding to a stromal marker, e.g., Fibroblast Activation Protein Alpha (FAP). In some embodiments, the cells may contain a protein circuit that contains at least two components, wherein one of the components binding-triggered transcriptional switch that is activated by binding to the stromal marker. The second component may be a nucleic acid encoding an immune receptor (e.g., a chimeric antigen receptor or TCR) that is activated by binding to a cancer-specific antigen and/or a pro-inflammatory cytokine.

Abstract: The present invention relates to the recognition of CSF1R as a marker of hematological cancer and thus relates to CSF1R targeting agents for the treatment of such cancers, in particular, AML. The invention also relates to a lymphocyte recombinantly expressing a chimeric antigen T cell receptor (CAR) specific for CSF1R, in particular, for use in the treatment of cancer characterized by the expression of colony stimulating factor 1 receptor (CSF1R). The present invention further relates to a CAR comprising an extracellular domain that specifically binds CSF1R, a transmembrane domain, and an intracellular T cell activating domain; as well as polynucleotides, vectors and host cells used in the production of the CAR. Further, methods for the production of such lymphocytes and a pharmaceutical composition comprising such lymphocytes are provided.

Abstract: An ROR1 CAR or ROR1/CD19 Dual CAR for the treatment of tumors. The T cells expressing ROR1 CAR or ROR1/CD19 Dual CAR can be stimulated by ROR1-positive or ROR1/CD19-positive cells, and have cytotoxicity against ROR1-positive or ROR1/CD19-positive cells.

Abstract: Provided herein are antibodies and chimeric priming receptors that bind PSMA and antibodies and chimeric antigen receptors that bind CA9. Also provided are systems of chimeric priming receptors that bind PSMA and chimeric antigen receptors that bind CA9, cells expressing such systems, and methods of use thereof.

Abstract: The present invention provides improved and/or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of cancer with a KRAS mutation with TILs as described herein in combination with KRAS inhibitors.

Abstract: Near-infrared (NIR) absorbing photosensitizers for imaging and treatment of cancer in a photodynamic therapy (PDT) are provided. Specifically, the NIR photosensitizers are mitochondria targeted and water-soluble, and used as a cytotoxic drug in a photodynamic therapy of the cancer. The NIR photosensitizers are activated with wavelengths of light, wherein the light penetrates through a body not just a skin. Hence the NIR photosensitizers aim to transform PDT from being a specialized treatment to a generally applicable one. PDT is almost completely non-invasive compared to current treatment methods.

Abstract: A kit for use in performing a cancer treatment, having a vial containing a phosphor-containing drug activator, wherein the phosphor-containing drug activator is present in the vial at a dosage level that is correlated with a size of tumor to be treated, and a container containing the vial; wherein the phosphor-containing drug activator contains an admixture of two or more phosphors capable of emitting ultraviolet and visible light upon interaction with x-rays; where the two or more phosphors include Zn2SiO4:Mn2+ and (3Ca3(PO4)2Ca(F, Cl)2:Sb3+, Mn2+) at a ratio (Zn2SiO4:Mn2+):(3Ca3(PO4)2Ca(F, Cl)2:Sb3+, Mn2+)) of from 1:10 to 10:1; wherein each of the two or more phosphors have at least one coating selected from an ethyl cellulose coating and a diamond-like carbon coating.

Abstract: The present disclosure provides materials and methods for preparing an antibody pharmaceutical formulation having a viscosity of 10 cP or less comprising exchanging a composition comprising the antigen binding protein with a diafiltration buffer comprising calcium at a temperature greater than 30° C.

Abstract: A leakage inhibiting agent includes a gelatin hydrolysate having a weight average molecular weight of 5000 or lees, wherein a degree of viscosity at 25° C. of a first solution obtained by dissolving the gelatin hydrolysate in phosphate buffered saline and adjusting the concentration of the gelatin hydrolysate to 40% by mans is 20 mPa·s or less.

Abstract: Polypeptides which can provide a senotherapeutic effect are provided herein. The polypeptides can be formulated for topical application and can be applied topically to a subject to provide a senotherapeutic effect in the subject or in the cells of the subject.

Abstract: In a preferred embodiment, there is provided a pharmaceutical coordination composition having a plurality of central atoms or ions, a multitopic ligand and one or more pharmaceutical compounds coordinated to at least one of the plurality of the central atoms or ions, wherein the multitopic ligand is coordinated to at least two of the plurality of central atoms or ions.

Abstract: Disclosed herein are novel bifunctional compounds formed by conjugating EGFR inhibitor moieties with E3 ligase Ligand moieties, which function to recruit targeted proteins to E3 ubiquitin ligase for degradation, and methods of preparation and uses thereof.

Abstract: The present disclosure provides, in one aspect, bifunctional compounds that can be used to promote or enhance degradation of certain circulating proteins. In certain embodiments, the circulating protein mediates a disease and/or disorder in a subject, and treatment or management of the disease and/or disorder requires degradation, removal, or reduction in concentration of the circulating protein in the subject. Thus, in certain embodiments, administration of a compound of the disclosure to the subject removes or reduces the circulation concentration of the circulating protein, thus treating, ameliorating, or preventing the disease and/or disorder.

Abstract: Provided herein are branched BAE/BTE-containing polymers useful as vehicles for the delivery of therapeutic agents, such as nucleic acids. The polymers form stable compositions and are suitable for the delivery of therapeutic agents via nebulization. Compositions of the disclosed polymers are capable of delivering therapeutic agents such as mRNA to lung epithelial cells.

Abstract: The disclosure provides a method of functionalising sodium carboxy methylcellulose (Na-CMC) which is a cellulose comprising at least one unit of Formula (0), where at least one G0 group is (I) and the remaining G0 groups are H. The disclosure also provides a CMC derivative product obtainable by this method, wherein the CMC derivative product comprises at least one unit of Formula (3), wherein: L is (II), n is an integer from 0 to 450; X is selected from (III), (IV), (V), (VI), (VII), (VIII), and (IX); L1 is a bond, alkylene, -(alkylene)O—*, —O(alkylene)-*, or -(alkylene)C(O)—*; wherein the*is the attachment to the cyclooctene or benzene ring; Z is —F, —Cl, —Br, or —I; R2 is —L2-M; L2 is an alkylene, -(alkylene)C(O)—*, -(alkylene)NHC(O)—*, —(CH2CH2O)mCH2—*, —CH2(OCH2CH2)m—*, arylene, or a bond, wherein the*is the attachment to M and m is an integer between 1 to 450; and M is a biomolecular unit.

Abstract: The invention features a composition comprising a potent cytotoxic compound and a pHILIP® peptide, where, e.g., the cytotoxic compound cannot be used alone due to a lack of targeting. pHILIP® peptide targets cytotoxic compounds to acidic diseased tissue, translocates cytotoxic compounds across plasma membranes into the cytosols of cells in acidic diseased tissues and induces cell death predominantly in the targeted acidic diseased tissue.

Abstract: The invention relates to isolated immunogenic peptides comprising a MHC class II T cell epitope, and immediately adjacent or separated from said epitope a H—X(0,2)-C—X(2)-[CST] or [CST]-X(2)-C—X(0,2)-H redox motif.

Abstract: Disclosed herein is a method of treating a tumor in a subject. The method comprises administering to the subject a molecular construct, which comprises an anti-CD38 antibody, and a plurality of lenalidomide molecules or hydrolyzed lenalidomide molecules linked to the anti-CD38 antibody. According to some embodiments of the present disclosure, the administration of the molecular construct gives rise to an effective amount of the lenalidomide molecules or the hydrolyzed lenalidomide molecules that is at least 1,000 times less than an effective amount of the lenalidomide molecule used alone or in combination with the anti-CD38 antibody for the treatment of the tumor.

Abstract: Described herein protein steroid conjugates that are useful, for example, for the target-specific delivery of glucocorticoids (GCs) to cells.

Abstract: Antibody molecule-drug conjugates (ADCs) that specifically bind to lipopolysaccharides (LPS) are disclosed. The antibody molecule-drug conjugates can be used to treat, prevent, and/or diagnose bacterial infections and related disorders.

Abstract: The invention relates to a conjugate containing a) an antibody or fragment of an antibody, and b) a specific protease for the immunoglobulin G (IgG) hinge region. The Invention also relates to a composition comprising at least one such conjugate, as well as to the use of this conjugate as a drug, in particular for the treatment of a disease caused by autoantibodies.

Abstract: Degrader-antibody conjugates (DACs) are described, comprising anti-TM4SF1 antibodies, and antigen-binding fragments thereof. Degrader molecules as described comprise a ubiquitin E3 ligase binding group (E3LB) and a protein binding group (PB). Linkers may be utilized between the antibodies and the degrader molecules (linker L1) and between the ubiquitin E3 ligase binding group (E3LB) and the protein binding group (PB) of the degrader molecule (linker L2). Methods of use of the DACs are also described.

Abstract: The present disclosure provides antibody-drug conjugate structures, that include cleavable linker having a sulfatase-cleavable moiety. The disclosure also encompasses methods of production of such conjugates, as well as methods of using the same.

Abstract: An antibody-drug conjugate (ADC) or a pharmaceutically acceptable salt thereof, is provided. The ADC includes a tetravalent monoclonal antibody conjugated to a cytotoxic drug by a chemical linker. The monoclonal antibody includes two long chains and four short chains. Each of the long chains includes a first segment and a second segment, the first segment located proximal to the N-terminus of the long chain, and the second segment located proximal to the C-terminus of the long chain. Each of the first segment and second segment pairs with one of the short chains to form an antigen-binding fragment domain, therefore forming four antigen-binding fragment domains having specificity toward the same antigen. Pharmaceutical composition including the ADC and methods of treating diseases using the compositions are also provided.

Abstract: The present invention provides an antibody against glypican-3 (GPC3) and application thereof, and the antibody comprises a single chain antibody and humanized antibody.

Abstract: Provided are a stem cell-nano anticancer drug complex in which an anticancer drug based on carbon nanotubes (CNT) and gold (Au) nano particles is loaded on the surface of stem cells, which can overcome side effects of conventional stem cells and targeting limitations of nano anticancer drugs and whose anticancer effect is very excellent, the use thereof, and a method for preparing the same.

Abstract: Disclosed herein are compositions and methods of modulating the expression of gene or the production of a protein by transfecting target cells with nucleic acids. The compositions disclosed herein demonstrate a high transfection efficacy and are capable of ameliorating diseases associated with protein or enzyme deficiencies.

Abstract: The present disclosure provides recombinant nucleic acids comprising one or more polynucleotides encoding a polypeptide; viruses comprising the recombinant nucleic acids; compositions and formulations comprising the recombinant nucleic acids and/or viruses; methods of their use (e.g., for the treatment of one or more conditions or diseases of the eye); and articles of manufacture or kits thereof.

Abstract: Disclosed herein are recombinant gene therapy vectors comprising a PTEN-induced kinase 1 (PINK1) encoding gene that is operatively linked to a promoter and methods of using the recombinant therapy vectors for inhibiting, reducing, or delaying degeneration or death of neurons of a subject.

Abstract: Disclosed herein are peptides and peptidomimetics that inhibit the progression of prostate cancer by up-regulating FLRT3. Also disclosed are methods for treating an FLRT3-attenuated cancer in a subject that involve administering to the subject the disclosed polypeptide or peptidomimetic or a polynucleotide encoding the disclosed peptide.

Abstract: Provided herein are modified adeno-associated virus (AAV) capsid proteins, particles, nucleic acid vectors, and compositions thereof, as well as methods of their use, such as in the treatment of neurological diseases and disorders. Specifically, the disclosure provides a modified AAV capsid protein comprising a non-native peptide within loop IV or loop VIII of the capsid protein. Further provided are non-native peptide sequences for insertion.

Abstract: Embodiments of the disclosure include methods and compositions for in situ cardiac cell regeneration, including transdifferentiation of cardiac cells to cardiomyocytes. In particular embodiments, in situ cardiac cell regeneration encompasses delivery of p63-TID and one or both of Hand2 and myocardin, and in specific embodiments further includes one or more of Gata4, Mef2c, and Tbx5, and/or one or more of ETV2 and VEGF. In specific aspects of the disclosure, adult cardiac fibroblasts are reprogrammed into cardiomyocytes using viral vectors that harbor p63-TID and one or both of the transcription factors Hand2 and myocardin.