295 results about "Immunologic Stimulation" patented technology

Disclosed is an immunity-inducing agent having excellent ease of production and high immunostimulatory activity, the immunity-inducing agent comprising, as an active component, a polynucleotide / peptide conjugate in which an antigenic peptide is covalently bound to a single-stranded polynucleotide or polynucleotide derivative. Also disclosed is a pharmaceutical composition comprising said immunity-inducing agent.

Apparatuses, systems and methods are provided for treating pulmonary tissues via delivery of energy, generally characterized by high voltage pulses, to target tissue using a pulmonary tissue modification system (e.g., an energy delivery catheter system). Example pulmonary tissues include, without limitation, those within the respiratory tract, particularly the epithelium (the goblet cells, ciliated pseudostratified columnar epithelial cells, and basal cells), lamina propria, submucosa, submucosal glands, basement membrane, smooth muscle, cartilage, nerves, pathogens resident near or within the tissue, or a combination of any of these. The systems may be used to treat pathogens, such as bacteria and viruses, particularly coronaviruses.

Provided are delivery immunostimulatory bacteria that have enhanced colonization of tumors, the tumor microenvironment and / or tumor-resident immune cells, and enhanced anti-tumor activity. The immunostimulatory bacteria are modified by deletion of genes encoding the flagella, or by modification of the genes so that functional flagella are not produced, and / or are modified by deletion of pagP or modification of pagP to produce inactive PagP product. As a result, the immunostimulatory bacteria are flagellin− and / or pagP−. The immunostimulatory bacteria optionally have additional genomic modifications so that the bacteria are adenosine or purine auxotrophs. The bacteria optionally are one or more of asd−, purI−, and msbB−. The immunostimulatory bacteria, such as Salmonella species, are modified to encode immunostimulatory proteins that confer anti-tumor activity in the tumor microenvironment, and / or are modified so that the bacteria preferentially infect immune cells in the tumor microenvironment, or tumor-resident immune cells, and / or are modified to induce less cell death in immune cells than in other cells. Also provided are methods of inhibiting the growth or reducing the volume of a solid tumor by administering the immunostimulatory bacteria.

The invention discloses a mouse model for treating in-situ pulmonary nodules by using bacterial lysates as well as a construction method and application of the mouse model. The method comprises the following steps: constructing an in-situ pulmonary nodule KT mouse model, instilling adenovirus, randomly dividing the model into an in-situ pulmonary nodule control group and a treatment group, performing bacterial lysate administration on mice in the treatment group at the maximum treatment dosage of 35mg / kg / d, and administering the same dosage of PBS solution to the control group. According to the invention, the possibility of killing cancer cells and preventing precancerous lesion progression by promoting autoimmunity of mice through oral immunostimulation drugs is provided for the first time, namely, the curative effect and mechanism of new drugs are researched through a mouse model, so that the clinical indications of the drugs are widened, and the blank field of clinical pulmonary nodule drug treatment is supplemented.

The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011 / 0150892 A1). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, is also provided.

The disclosure relates to cancer ribonucleic acid (RNA) vaccines, as well as methods of using the vaccines and compositions comprising the vaccines. In particular, the disclosure relates to concatemeric mRNA cancer vaccines encoding several cancer epitopes on a single mRNA construct, i.e. poly-epitope mRNA constructs or poly-neo-epitope constructs. The disclosure further relates to p53 and KRAS mutations, as well as incorporation of immune enhancers such as STING, e.g. mRNA constructs further encoding an immune stimulator or adjuvant. The disclosure further relates to inclusion of universal T cell epitopes, such as tetanus or diphtheria toxins to elicit an enhanced immune response.

Embodiments of the present invention generally relate to novel immunostimulatory compositions of use to stimulate non-specific immune responses in a subject. In certain embodiments, immunogenic compositions disclosed herein can be directed to use in the eye of a subject. In some embodiments, the immunogenic compositions disclosed herein enhance non-specific immune responses in the eye of a subject to treat or reduce the risk of onset of an eye condition. In other embodiments, compositions disclosed herein can be used to treat eye infections due to a microorganism, tumors of the eye, as well as, chronic wounds or infections of the eye. In some embodiments, immunogenic ocular formulations disclosed herein include combinations of agents for prolonged exposure to the eye for improved outcomes.

Provided is an siRNA that inhibits the expression of an MMP7 gene, which siRNA contains a sense strand and an antisense strand. The provided siRNA has good stability, excellent MMP7 gene inhibitory activity, and negligible cytotoxicity and immunostimulation, and can significantly reduce MMP7 protein levels at the animal level. The siRNA has important clinical values in the treatment of diseases or conditions benefiting from the reduction of MMP7 levels or the inhibition of MMP7 expression.

A varicella-zoster vaccine composition and use thereof, belonging to the technical field of biological vaccines. The composition comprises a VZV gE antigen and a CpG ODN adjuvant and further comprises an aluminum adjuvant. The nucleotide sequence of the CpG ODN adjuvant is set forth in SEQ ID NO: 1. The CpG ODN adjuvant with a specific nucleotide sequence has better immunostimulatory activity. The provided varicella-zoster vaccine composition can generate a higher humoral immune response earlier and induce protective immunity in advance for at least one month. One immunization can reach or be close to the antibody level of two immunizations of the Shingrix vaccine. Moreover, the longer-time stable high-humoral immunity level can be kept, and cellular immunity can also be generated.

The invention discloses a varicella zoster vaccine composition and application thereof, and belongs to the technical field of biological vaccines, the composition comprises a VZV gE antigen, a CpG ODN adjuvant and an aluminum adjuvant, and the nucleotide sequence of the CpG ODN adjuvant is shown as SEQ ID NO: 1. According to the invention, the CpG ODN adjuvant with a specific nucleotide sequence is selected, so that the immunostimulatory activity is better; the varicella zoster vaccine composition provided by the invention can generate high humoral immune response earlier, and induces protective immunity for at least one month in advance; the antibody level of twice immunization of a Shigrix vaccine can be reached or close to once immunization, the stable high humoral immune level for a long time can be kept, and meanwhile cellular immunity can be generated.

The invention belongs to the technical field of biological medicines, and particularly discloses a collagen peptide composition for enhancing immunostimulation osteoblast synthesis and a preparation method thereof, the collagen peptide composition comprises the following components by mass: 0.05-0.2% of taurine, 0.1-1% of vitamin C, 5-20% of type II collagen peptide, 5-20% of type III collagen peptide, and the balance of bovine bone collagen peptide. On the basis of the bovine bone collagen peptide, under the action of the taurine, the vitamin C, the II type collagen peptide, the III type collagen peptide and the red date extract, immunity can be effectively improved, osteoblasts are stimulated to synthesize the collagen peptide, and therefore the bone mineral density is effectively increased, and the osteoporosis is reduced. Wherein the red date extract and the bovine bone collagen peptide have a remarkable synergistic effect.

The invention belongs to the technical field of biological medicine, and particularly relates to an adjuvant composition, a respiratory syncytial virus vaccine composition and application thereof. In the invention, the aluminum adjuvant and the specific CpG ODN adjuvant form the adjuvant composition according to a specific proportion, and the respiratory syncytial virus (RSV) vaccine composition comprising the adjuvant composition has better immunostimulatory activity, can generate higher humoral immune response earlier, and can maintain higher cellular immune response for a long time. The human RSV vaccine can generate immune response which is comparable to that of a marketed vaccine Arexvy, and is a safe, effective and promising human RSV candidate vaccine.

Compositions containing a nucleic acid nanostructure having a desired geometric shape and an antigen and / or immunostimulatory agent(s) bound to its surface are provided. The nanostructure design allows for control of the relative position and / or stoichiometry of the immunostimulatory agent(s) bound to its surface. The antigen and / or immunostimulatory agent(s) displayed on the nanostructure surface are arranged with the preferred number, spacing, and 3D organization to elicit a robust immune response. The displayed antigen can be eOD-GT8. The immunostimulatory agent can be, e.g., T cell epitope such as a pan HLA DR-binding epitope (PADRE) and / or a lectin such as MBL or C3, or ligand thereof such as a glycan including mannose. Also provided are antigen-T cell epitope fusions such as eOD-PADRE and nanostructures presenting the same. The immunostimulatory compositions may thus be useful as immunogens, vaccines, adjuvants, and the like. Methods of inducing immune responses are also provided.

The invention discloses a bacterial outer membrane vesicle protein drug delivery system derived from attenuated salmonella as well as a preparation method and application of the bacterial outer membrane vesicle protein drug delivery system. According to the bacterial outer membrane vesicle protein drug delivery system, plug-and-play of a protein drug can be realized on the surface of a bacterial outer membrane vesicle. The invention constructs a bacterial outer membrane vesicle protein drug delivery system. OmpA of attenuated salmonella typhimurium VNP20009 is knocked out, recombinant OmpA of SpyTag inserted into an extracellular ring structural domain is supplemented, fusion protein of SpyCatcher and a protein drug is displayed on the surface of the bacterial outer membrane vesicle by means of the property that an isopeptide bond is spontaneously formed between SpyTag and SpyCatcher, the preparation method is simple and easy to operate, various proteins are displayed on the surface of the bacterial outer membrane vesicle, and the bacterial outer membrane vesicle has a good application prospect. And protein drugs are efficiently protected and loaded. And by combining the immunostimulation characteristic of the bacterial outer membrane vesicles, efficient treatment of tumors is realized.

The invention provides ROS (reactive oxygen species) temperature double-sensitive injectable immunocompetence polyamino acid hydrogel and application thereof. The hydrogel can be independently gelled, the drug loading capacity is high and adjustable, and the hydrogel has temperature response, reactive oxygen species (ROS) response and immunostimulatory activity and can be injected. Through temperature response, the hydrogel is in a solution state under a low-temperature condition and is easy to inject, and the hydrogel can be quickly gelatinized under a body temperature condition to locally form a medicine storage cavern, so that the release time of the medicine is prolonged. Due to ROS response, the hydrogel achieves intelligent response to drug release by responding to a high-active oxygen microenvironment of a tumor site, and selective drug release is achieved. Due to the immunocompetence, the hydrogel can positively respond to a high-active-oxygen local microenvironment of a tumor site, R848 is released to stimulate the activity of host immune cells, and the anti-tumor effect is improved. The hydrogel can be simply and conveniently mixed with other treatment drugs for combined treatment, so that the tumor treatment effect is improved.

To provide a novel stereoselective method for producing a cyclic dinucleotide derivative that can be used for an antibody-immunostimulator conjugate, and a production intermediate thereof, and to provide methods for producing a cyclic dinucleotide-linker and antibody-immunostimulator conjugate using the production method.SOLUTION: The present invention relates to a method that makes it possible to produce, in large amounts and with high yield, a cyclic dinucleotide derivative having a desired steric configuration, by using an optically active phosphitylation agent twice, during coupling and cyclization.SELECTED DRAWING: None

The present invention relates to a bispecific antibody that specifically binds to VISTA and MSLN, and uses thereof. The bispecific antibody exhibits significant immuno-oncological activity and ADCC activity compared to a monospecific antibody, degrades target proteins through internalization activity, and possesses tumor-targeting ability, and thus can be advantageously used for the prevention or treatment of various cancers.

Provided herein are cytokine-encoding nucleic acid molecules, such as recombinant expression vectors, and uses thereof to make modified tumor infiltrating lymphocytes (TILs), wherein the modified TILs include one or more immunomodulatory agents (e.g, cytokines) associated with their cell surface. The immunomodulatory agents associated with the TILs provide a localized immunostimulatory effect that can advantageously enhance TIL survival, proliferation and / or anti-tumor activity in a patient recipient. As such, the compositions and methods disclosed herein provide effective cancer therapies.

The present invention is directed to a method for treating cancer by delivering lipid-nanoparticles (LNPs) encapsulating immunostimulant mRNA and bispecific antibody mRNA to cancer cells or intratumorally. The method comprising the step of administering mRNA-encapsulated LNPs to a tumor lesion of a subject having cancer. The immunostimulant mRNA-LNP activates immune cells around tumor, which work together with mRNA-LNP encoding bispecific antibody and PBMC to effectively target local and distant metastatic tumors. Preferred immunostimulants are GM-CSF and IL-12, and its combination.

The invention relates to detection of vaccine immune effects, in particular to a Marek's disease virus specificity IFN-gamma sandwich ELISA method and application thereof. The invention provides a Marek's disease virus specific T cell immune stimulator, and the amino acid sequence of the Marek's disease virus specific T cell immune stimulator is shown as SEQ ID NO: 1 or SEQ ID NO: 3. The invention further provides a method for detecting the cellular immune level after Marek's disease vaccine immunization. The Marek's disease virus specific T cell immunostimulant can effectively stimulate cell-mediated immune response, initiate and activate MDV specific T cells, so that the Marek's disease virus specific T cells generate Marek's disease virus specific IFN-gamma, and the Marek's disease virus specific T cell immunostimulant has a good application prospect in Marek's disease vaccine immune level detection.

Disclosed are compounds, compositions, and methods relating to epitope-targeted immunostimulants (EPis), which comprise a synthetic peptide ligand and an antibody-recruiting moiety. The peptide ligand binds an epitope on a target and the antibody-recruiting moiety recruits antibodies to the target when the EPI is bound to the epitope on the target. Also disclosed are compositions comprising any of the disclosed EPis. Also disclosed are methods of stimulating an immune reaction to a microorganism or other pathogen in a subject where an EPI is administered to the subject. Also disclosed are methods of identifying the peptide ligand by using multi-omic analysis.

The present invention relates to a composition for enhancing immunity, containing, as an active ingredient, a polysaccharide enzyme-treated product derived from a mixed extract of Angelica gigas, Cnidium officinale, and Paeonia lactiflora, or a novel purified polysaccharide fraction thereof. The composition for enhancing immunity according to the present invention, comprising the polysaccharide enzyme-treated product of the mixed extract of Angelica gigas, Cnidium officinale, and Paeonia lactiflora or the novel purified polysaccharide fraction thereof, is composed of specific types and contents of sugars and significantly increases the activity of macrophages, splenocytes, and NK cells upon application thereto, thereby being applicable as an immunopotentiator or a composition for enhancing immunity.

The present invention is directed to a method for treating cancer by delivering lipid-nanoparticles (LNPs) encapsulating immunostimulant mRNA and bispecific antibody mRNA to cancer cells or intratumorally. The method comprising the step of administering mRNA-encapsulated LNPs to a tumor lesion of a subject having cancer. The immunostimulant mRNA-LNP activates immune cells around tumor, which work together with mRNA-LNP encoding bispecific antibody and PBMC to effectively target local and distant metastatic tumors. Preferred immunostimulants are GM-CSF and IL-12, and its combination.

The present invention relates to the technical field of biomedicine, and in particular to an adjuvant composition, a respiratory syncytial virus (RSV) vaccine composition, and a use thereof. An aluminum adjuvant and a CpG ODN adjuvant are combined in proportion to form an adjuvant composition. An RSV vaccine composition comprising the adjuvant composition has better immunostimulatory activity, can enable early induction of a high humoral immune response, can maintain a strong cellular immune response for a long time, can produce an immune response comparable to that of a licensed vaccine Arexvy, and is a safe, effective and promising human RSV candidate vaccine.

Disclosed are compounds, compositions, and methods relating to epitope-targeted immunostimulants (EPIs), which comprise a synthetic peptide ligand and an antibody-recruiting moiety. The peptide ligand binds an epitope on a target and the antibody-recruiting moiety recruits antibodies to the target when the EPI is bound to the epitope on the target. Also disclosed are compositions comprising any of the disclosed EPIs. Also disclosed are methods of stimulating an immune reaction to a microorganism or other pathogen in a subject where an EPI is administered to the subject. Also disclosed are methods of identifying the peptide ligand by using multi-omic analysis.

The present invention relates to the field of vaccines, and in particular to a novel adjuvant polypeptide sequence and a use thereof. The adjuvant polypeptide sequence provided by the present invention comprises amino acid sequences of tetanus toxoid epitopes P2 and P16 and further comprises amino acid sequences of P30 and / or PX. The adjuvant polypeptide sequence aims to expand the coverage population of immune responses by increasing epitope diversity. In addition, the present invention uses an LNP (lipid nanoparticle) delivery system to introduce an mRNA encoding an adjuvant polypeptide and an initial antigen protein into a human body, thereby improving the immunostimulatory ability of the initial antigen. The adjuvant polypeptide sequence provided by the present invention and the initial antigen sequence are preferably fused, thereby simplifying the composition of mRNA in a nucleic acid vaccine and reducing the complexity of vaccine preparation.

To provide an immunostimulating composition.SOLUTION: An immunostimulating composition comprises, as an active ingredient, a bacterium that is phagocytosed by plasmacytoid dendritic cells (pDC) at or above a predetermined level.SELECTED DRAWING: None

What is described is a peptide for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy. Furthermore, such a peptide is described for use in the reduction of side-effects in form of immunostimulatory reactions / effects which occur with gene therapy, wherein the peptide is coupled to a nucleic acid molecule used in gene therapy, wherein the immunostimulatory reactions / effects are induced by activation of IFIT1 / 2, IRF9, TLR3, TLR7, TLR8 or PKR.

The invention provides a preparation method and application of a nitrogen-containing heterocyclic micromolecule modified polyethyleneimine polymer derivative. Compared with a polyethyleneimine polymer, the nitrogen heterocyclic ring micromolecule modified polyethyleneimine polymer derivative provided by the invention has immunostimulatory activity. Besides, the polymer derivative material provided by the invention can be simply mixed with a protein antigen to form nanoparticles, so that efficient loading of the protein antigen is realized, the delivery efficiency of the protein antigen to lymph nodes is improved, and the polymer derivative material can be used for preparing a novel nano vaccine preparation.