182 results about "Immune Stimulation" patented technology

The invention discloses an engineered autologous tumor tissue scaffold and application thereof, and the engineered autologous tumor tissue scaffold is prepared by performing specific treatment on autologous tumor tissue to induce immunogenic cell death of the tumor tissue, and then sequentially performing freezing and drying steps; the engineered autologous tumor tissue scaffold can be used for loading dendritic cells and constructing personalized tumor vaccines. According to the stent, autologous tumor tissue is adopted, so that a specific and comprehensive tumor antigen pedigree is reserved, and multi-epitope immunostimulation is provided; and meanwhile, excellent biocompatibility is ensured, the immunological rejection risk is reduced, and relatively high safety is ensured.

Disclosed are methods of augmenting efficacy of oncology therapies by providing reprogrammed cells such as personalized regenerative cells that modulate the tumor microenvironment. In one embodiment, somatic cells are dedifferentiated into OCT-4 expressing cells and endowed with tumor homing properties through culture or gene engineering. Once a stable population of tumor homing cells is established, such cells are made to express immune stimulating agents constitutively, or selectively upon entering the cancer microenvironment. Selective expression of immune stimulatory agents can be induced by exposure to hypoxia, acidosis, immune suppressive signaling or inflammatory signaling.

To provide an oral composition for effectively activating plasmacytoid dendritic cells (pDCs).SOLUTION: An oral composition for activating plasmacytoid dendritic cells (pDCs), comprising Lacticaseibacillus rhamnosus CRL1505, wherein the composition is preferably intended for immune activation. The oral composition for activating pDCs is considered to: regulate both innate immunity and acquired immunity; act on an overall immune function, maintain a normal immune function, and maintain good physical conditions. The present invention also provides an oral composition for immune activation characterised in that it comprises Lacticaseibacillus rhamnosus CRL1505, wherein the immune activation is intended for symptoms such as nasal congestion.SELECTED DRAWING: Figure 1

The invention is applicable to the technical field of medical instruments, and provides a subskull epidural micro-invasive flexible brain-computer interface electrode, which comprises a plurality of electrode branches, each electrode branch comprises a linear flexible main body, and the flexible main body comprises a micro power supply circuit and a signal circuit which are solidified. A plurality of electrode units are arranged on the micro power supply circuit and the signal circuit at intervals, and the electrode units are electrically connected with the micro power supply circuit and the signal circuit. The brain-computer interface electrode is in a flexible line type, can be implanted into the middle artery of the meninx, does not need craniotomy, is a micro-invasive brain-computer interface, has data monitoring accuracy close to that of an invasive brain-computer interface, does not need to worry about inflammatory response, immunostimulation, biocompatibility, brain tissue damage and other adverse factors after long-term implantation, and is suitable for popularization and application. And the thrombogenic risk of a vein stent brain-computer interface does not exist.

The invention belongs to the technical field of biological medicine, and particularly discloses a composite vaccine adjuvant as well as a preparation method and application thereof. The composite vaccine adjuvant provided by the invention is an oil-in-water emulsion, and simultaneously contains squalene, polysorbate 80, sorbitan trioleate, polyinosinic acid (Poly I: C) and CpG oligodeoxynucleotide (CpG-ODN). The sequence-optimized CpG-ODN and Poly I: C are used in a specific emulsion system in a combined mode, a remarkable synergistic immune enhancement effect can be generated, the induced humoral immunity and cellular immunity response level is remarkably higher than the sum of the effects when all the components are independently used, and the composite adjuvant is good in stability, high in immunostimulatory activity and suitable for clinical application. The immune effect can be remarkably improved by combined application with various vaccine antigens. The invention also provides a preparation method and application of the composite vaccine adjuvant.

The invention relates to the technical field of biological pharmacy, and discloses a QS-21 saponin adjuvant as well as a preparation method and application thereof, the adjuvant is a composite liposome and comprises a liposome skeleton composed of distearoyl phosphatidylcholine and cholesterol, and QS-21 saponin, monophosphoryl lipid A and a local anesthetic are jointly entrapped in the liposome skeleton. The problem that high reactogenicity and immunogenicity of potent adjuvants are difficult to consider at the same time is solved, the immunostimulation component and the pain inhibition component are jointly entrapped in the same nano-carrier, collaborative delivery in injection local is achieved, and therefore pain and swelling caused by the adjuvants are accurately inhibited. The co-entrapment structure avoids the potential inhibition effect of the free anesthetic on the immune system, the potent body fluid and cellular immune enhancement activity of the adjuvant is completely reserved, and a new technical scheme is provided for developing vaccines with high safety and strong immune efficacy.

This disclosure relates to polyethylene glycol (PEG)-functionalized nanoparticles comprising a functional agent, and preparation methods, properties and applications thereof. The nanoparticle represented by PEG-L-G / P, comprising a type of hydrophilic PEG, a hydrophobic functional agent G, which are covalently linked by L: a linker or a chemical bond, and a type of hydrophobic polymer P. The G and P form the hydrophobic core, while the PEG constitutes the hydrophilic outer layer of the nanoparticle in an aqueous medium. The functional agent comprises one or more functional compounds including a therapeutic drug, an imaging diagnostic agent, a photoelectric responsive diagnostic agent, an immune-stimulating agent, or a combination thereof. The nanoparticles comprising such functional agent can offer various applications in multiple biomedical fields.

Disclosed herein are compositions and methods of use thereof for the prevention of mastitis in dairy cattle. The compositions and methods can have immunostimulant effectiveness against mastitis-causing bacteria. In particular embodiments, the methods include preventing mastitis infection by intramammary infusion of a disclosed composition at dry-off.

The invention relates to the technical field of medicinal chemistry, and provides a TLR4 agonist, application thereof and a vaccine composition. The TLR4 agonist is a compound with a structure as shown in a formula 1 or a pharmaceutically acceptable salt thereof, the compound is glucosamine aminoalkyl 4-phosphate series molecules derived from MPL-12 structure modification, and the series molecules have enhanced immunostimulatory activity and selective immune response induction capability.

This disclosure relates to polyethylene glycol (PEG) -functionalized nanoparticles comprising a functional agent, and preparation methods, properties and applications thereof. The nanoparticle represented by PEG-L-G / P, comprising a type of hydrophilic PEG, a hydrophobic functional agent G, which are covalently linked by L: a linker or a chemical bond, and a type of hydrophobic polymer P. The G and P form the hydrophobic core, while the PEG constitutes the hydrophilic outer layer of the nanoparticle in an aqueous medium. The functional agent comprises one or more functional compounds including a therapeutic drug, an imaging diagnostic agent, a photoelectric responsive diagnostic agent, an immune-stimulating agent, or a combination thereof. The nanoparticles comprising such functional agent can offer various applications in multiple biomedical fields.

The present invention relates to a compound represented by formula (I) or a stereoisomer, tautomer, solvate or pharmaceutically acceptable salt of a compound represented by formula (I), TIFF2026503201000033.tif3981X1, X2 and X3 are each independently an optionally substituted C1-C 15 alkylene, and R and R are each independently an optionally substituted C-C 40 Alkyl, optionally substituted C-C 40 Heteroalkyl, optionally substituted C-C 40 Alkenyl, optionally substituted C-C 40 Heteroalkenyl, optionally substituted C-C 40 Alkynyl or optionally substituted C-C 40 The present invention provides a compound comprising heteroalkynyl, wherein R3, R4, R5, and R6 are each independently H, halogen, or optionally substituted C1-C3 alkyl, and the substituents are independently selected from halogen, -OH, -SH, -NH2, -NO2, cyano, and C1-C3 alkyl, which has the advantages of low cytotoxicity, strong delivery ability, and strong immunostimulatory effect.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula:wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

The invention relates to the technical field of biological medicine, and discloses a nano composite adjuvant as well as a preparation method and application thereof. The composite adjuvant mainly comprises a TLR9 agonist CpG ODN, a nanoscale liposome, a cationic lipid DOTAP and a high-efficiency immunologic stimulant QS-21, several adjuvant components are prepared into the stable and uniform nanoscale liposome by adopting a microfluidic synthesis method, CpG is wrapped inside the nanoscale liposome, QS-21 is adsorbed outside the nanoscale liposome, a stable immunologic stimulation compound is formed, and the immunologic stimulant can be used for immunologic detection of the TLR9 agonist CpG ODN, the cationic lipid DOTAP and the high-efficiency immunologic stimulant QS-21. All the components have a remarkable synergistic effect, and are matched with corresponding antigens to generate strong and lasting cellular immune and humoral immune responses.

Disclosed is a method for evaluating the immunostimulatory capacity of a target substance, the method including a contacting step in which a human plasmacytoid dendritic cell line is cultured in the presence of the target substance, wherein the human plasmacytoid dendritic cell line is the CAL-1 cell line (accession number FERM BP-10914), and the CAL-1 cells are in a starvation state during at least part of the contacting step.

The application discloses a method for preparing cell-derived exosomes and products and applications thereof, and the method comprises the following steps: co-culturing immune-activated programmable cells with a stimulating agent with immune-activation effect, and collecting the cell-derived exosomes with immune activity by a natural secretion collection method or an artificial extrusion collection method. The application has safe and controllable local immune activation, and the immune activation strategy based on the exosomes fully overcomes the safety bottleneck of traditional live bacterial preparations in tumor treatment. By replacing live bacteria with engineered exosomes, not only potential risks such as systemic inflammatory response and infection are effectively avoided, but also the local controllability of immune stimulation signals is ensured, the precise activation and directional regulation of tumor region immune cells are realized, the tumor microenvironment is reshaped, the anti-tumor effect is strengthened, and the broad-spectrum cross-tumor potential is verified across models.

This invention relates to the field of biopharmaceutical technology, disclosing a QS-21 saponin adjuvant, its preparation method, and its applications. The adjuvant is a composite liposome comprising a liposome backbone composed of distearate phosphatidylcholine and cholesterol, with QS-21 saponin, monophosphatidyllipid A, and a local anesthetic co-encapsulated therein. This invention solves the common problem of high reactivity and immunogenicity in potent adjuvants by co-encapsulating immunostimulatory and analgesic components on the same nanocarrier, achieving synergistic delivery at the injection site, thereby precisely inhibiting adjuvant-induced pain and swelling. This co-encapsulation structure avoids the potential inhibitory effect of free anesthetics on the immune system, fully preserving the adjuvant's potent humoral and cellular immune-enhancing activity. This invention provides a new technical solution for developing vaccines with both high safety and strong immunogenicity.

Contemplated treatments and methods produce substantially increased quantities of memory T-cells and a persistent immune response by subcutaneous and / or subdermal co-administration of (1) a vector comprising a recombinant nucleic acid that encodes a cancer associated epitope, a cancer specific epitope, and / or a neoepitope, (2) an immune stimulating cytokine, and (3) a checkpoint inhibitor. Most typically, the co-administration is performed at substantially the same location, preferably within 1-21 days from each other, and the vector is an adenoviral expression vector, for example, included in a viral particle such as an AdV5 virus with a deletion of the E2b gene.

The present disclosure provides compositions and methods for the delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse. The compositions comprise (i) a structure comprising an injectable polymer or scaffold comprising pores; (ii) lymphocytes disposed within the structure, (iii) at least one lymphocyte-adhesion moiety associated with the structure; and (iv) at least one lymphocyte-activating moiety associated with the structure, and optionally an immune stimulant.

Aminopyrimidine containing compounds that inhibit both Mer tyrosine kinase (MerTK) activity and Tyro3 kinase activity are disclosed herein. Additionally disclosed are methods of synthesis and use of the aminopyrimidine containing compounds as anti-cancer agents, immunostimulatory and immunomodulatory agents, anti-platelet agents, anti-infective agents, and as adjunctive agents.

The present invention provides compositions and methods for treating cancer or a metastasis thereof in a subject. In some embodiments, the methods involve administering a composition comprising therapeutically effective amount of at least one immune stimulator to the subject. In some embodiments, a combination of at least two immune stimulators is used for the treatment. In some embodiments, the combination includes an alpha thymosin peptide and an additional immune stimulator, and / or optionally one or more additional anti-cancer agents.

The invention provides annular functional nucleic acid as well as a preparation method and application thereof, functional nucleic acid and annular nucleic acid are combined, a DNA template assembly is matched with an enzymatic coupling method, a single-stranded annular nucleic acid is firstly prepared, a corresponding outer side short chain is synthesized, a functional nucleic acid drug is coupled to the outer side short chain, reaction conditions are optimized and screened, and the annular functional nucleic acid is obtained. The prepared annular functional nucleic acid has the characteristics of being adjustable in size, adjustable in valence state (multivalent or multiple), high in stability, capable of being chemically coupled with drugs or chimeric with the drugs and the like, a novel annular multivalent functional nucleic acid technology is created, and the targeting property and the stability of nucleic acid drugs can be remarkably improved; a nucleic acid drug development platform o-FLARE with efficient targeting, immune excitation and protein degradation functions is constructed.

Provided herein are immune-stimulating anti-HBsAg antibody conjugates, such as a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of use thereof for treating, preventing, or alleviating one or more symptoms of HBV infection.

The present invention relates to compositions comprising an inactivated Mycobacterium or an immunogenic fraction thereof, for use in the prevention of an infection in a subject, wherein the infection is selected from the group consisting of a protozoan parasitic infection and a bacterial infection, with the proviso that the infection is not caused by a Mycobacterium.

Provided herein are immune stimulating anti-HBsAg antibody conjugates, e.g., a compound of Formula (I), and pharmaceutical compositions thereof. Also provided herein are methods of their use for treating, preventing, or ameliorating one or more symptoms of an HBV infection.

The invention discloses a Brucella vaccine of recombinant adenovirus based on BP26 and IFNG and application, and belongs to the technical field of biological medicine. In order to develop a safe and effective brucella recombinant adenovirus vector vaccine, a brucella immunodominance antigen is designed through a genetic engineering technology, a recombinant adenovirus of an antigen-coupled molecular adjuvant IFN-gamma is constructed, and the constructed recombinant adenovirus is identified through PCR, WB, an electron microscope and the like. And the immune stimulation capability and the protective efficacy of the brucella recombinant adenovirus vector vaccine are evaluated by verifying the cellular immune response level and the humoral immune response level induced by the vaccine at a mouse level and the challenge protection efficiency, so that a foundation is laid for research and development of a brucella recombinant adenovirus candidate vaccine.

Two-component vaccine formulations and methods are contemplated where the vaccine has an adjuvant component and a therapeutic component. The therapeutic component comprises preferably a recombinant therapeutic virus encoding a therapeutic antigen while the adjuvant component comprises a non-host cell or immune stimulating portion thereof. Notably, use of the adjuvant component will result in significant uptake of the therapeutic component into immune competent cells, even in the absence of receptors for entry of the therapeutic component. In addition, such adjuvant also stimulates expression of the therapeutic antigen.

The invention provides a nucleic acid aptamer, and the nucleotide sequence of the nucleic acid aptamer is as shown in SEQ ID No: 1, or a sequence having 80% or more of identity with the nucleotide sequence. The nucleic acid aptamer successfully screened out in the invention has good affinity and specificity with CD40, and the binding capacity of the nucleic acid aptamer can be comparable with that of an antibody. In the functional level, the nucleic acid aptamer can be effectively combined with DC2.4 cells expressing CD40 and up-regulate the expression of related genes; the compound also shows remarkable immunostimulatory activity in an animal model, and shows a synergistic effect when being combined with an immunostimulant. The invention provides an important basis for subsequent development and transformation application of the CD40 nucleic acid aptamer, and also provides a new candidate tool and technical support for drug research and development based on a CD40 target spot.

A system and corresponding method are provided for identifying a subpopulation of cancer patients who are immunotherapy respondents. An effective method of assessing neoantigen presentation is provided. A vaccine composition is also provided. The vaccine composition is prepared by feeding data for a subject with a type of cancer into a predictive model and scoring neoantigens that occur in data for the subject for one or more parameters. One or more vaccine compositions to be administered to the subject are prepared for one or more somatic mutations for one or more neoantigens that satisfy an immune stimulation threshold.

Provided are siRNA and its conjugate for inhibiting AGT gene expression, comprising a sense strand and an antisense strand. The provided siRNA, siRNA conjugate, and pharmaceutical composition have good stability, excellent AGT gene inhibition activity, and satisfactory cytotoxicity and immunostimulation.

The invention discloses a cyclic dinucleotide compound as well as a conjugate and application thereof, and particularly discloses an antibody-immunostimulatory conjugate as shown in a formula II or pharmaceutically acceptable salt thereof. The antibody-immunostimulation conjugate provided by the invention has good tumor specificity and has an obvious inhibition effect on tumors. # imgabs0 #