39 results about "Immune Evasions" patented technology

We describe compositions of DNA donor molecules compatible with various gene insertion methods with major advantages for delivery, nuclear localization, and immune evasion. The modified DNA donor molecules are largely single stranded but contain short regions of double-strand DNA to reconstitute enzyme binding sites, and can be combined with other approaches to enhance donor recruitment into the nucleus.

The present invention provides compositions for the prevention and treatment of genital herpes, comprising nucleoside modified mRNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

Therapeutic agents that can place bulky proteins, such as CD45, CD148, and CD43, at the center of the cellular interface between graft cells and CD45-positive host effector cells (e.g., T cells, NK cells, B cells, or dendritic cells) are disclosed, as are methods of their use and products made with such therapeutic agents. The therapeutic agents prevent or inhibit the formation of functional immunological synapses (including physiological SMACs). They also result in the continuous dephosphorylation of signaling pathways.

This invention provides an H3N2 influenza mRNA vaccine targeting the tandem HA and NA proteins and its preparation method, relating to the field of vaccine preparation technology. The H3N2 influenza mRNA vaccine is obtained by linking the conserved amino acid sequences of HA and NA of H3N2 with GGGSGGGSGGGSGGGS, and the amino acid sequence of the H3N2 influenza mRNA vaccine is shown in SEQ ID NO.1, and the nucleic acid sequence is shown in SEQ ID NO.2. This invention overcomes the shortcomings of existing technologies, improves the protective effect of the vaccine against H3N2 influenza, and enables it to better cope with immune evasion from the latest emerging H3N2 variants.

This invention belongs to the field of biopharmaceutical technology and specifically relates to the use of NT5M in the preparation of a drug for the treatment of pancreatic cancer. The invention reveals that NT5M is a key metabolic regulator in PAAD, influencing tumor progression, immune regulation, and drug sensitivity. Low NT5M expression is associated with poor prognosis, while its overexpression inhibits cell migration, invasion, and PD-L1-mediated immune evasion, highlighting its potential as a tumor suppressor in PAAD. It can serve as both a prognostic biomarker and a potential therapeutic target, providing a new treatment strategy for PAAD patients.

The present invention provides a method for treating or alleviating a symptom of a disorder, e.g., immune evasion, cancer-cell induced immune dysfunction, reduced immune response, lowered inflammation, decreased expression of a major histocompatibility complex (MHC), or cancer, characterized by aberrant, misregulated, or increased Enhancer of Zeste Homolog 2 (EZH2) activity in a cell or subject in need thereof by contacting the cell or administering to the subject a therapeutically effective amount of an EZH2 inhibitor.

The invention belongs to the technical field of gene engineering, and particularly relates to a construction method and application of a recombinant vector based on bCoro1a gene 3 'UTR editing. The recombinant vector consists of an upstream homologous arm of a targeting site, 3 'UTR inserted into a target sequence, 200bp of a nucleotide tailing signal of bCoro1a, a selection marker and a downstream homologous arm of the targeting site; the targeting site is the 29 or 70 site of the 3 'UTR of the bCoro1a gene; the sequence of the 3 'UTR of the bCoro1a gene is as shown in SEQ ID NO. 48; the selection marker comprises enhanced green fluorescent protein and puromycin, the bCoro1a 3 'UTR edited gene expression regulation and control system is based on bCoro1a 3' UTR edited gene expression regulation and control system, and the expression level of bCoronin-1A is reduced in a targeted manner by inserting a specific bta-miR-27b target sequence into 3 'UTR, so that M.tb immune escape is inhibited, and the M.tb infection resistance of a host is improved.

We describe compositions of DNA donor molecules compatible with various gene insertion methods with major advantages for delivery, nuclear localization, and immune evasion. The modified DNA donor molecules are largely single stranded but contain short regions of double-strand DNA to reconstitute enzyme binding sites, and can be combined with other approaches to enhance donor recruitment into the nucleus.

This disclosure provides compositions and methods of making cells, such as allogenic cells, engineered to evade host immune responses, particularly from T cells and natural killer cells, and populations thereof. The compositions and methods for making engineered cells include making genetic modifications that reduce or eliminate the expression of an NKG2D ligand or integrate sequences encoding HLA molecules, such as HLA-E or HLA-G. Such modifications can enhance the survival of the engineered cells within a host without impeding their ability to differentiate into functional cell types, such as cardiomyocytes.

The invention discloses a preparation method of a bionic magnetic nano-motor mixed and wrapped by a neutrophile granulocyte membrane and a stem cell exosome. The bionic magnetic nano-motor comprises the neutrophile granulocyte membrane, the stem cell exosome, a polylactic acid-glycolic acid copolymer and an anti-inflammatory drug. According to the method, a layer of polylactic acid-glycolic acid copolymer is wrapped outside magnetic ferroferric oxide nanoparticles and an anti-inflammatory drug by utilizing an ultrasonic emulsification method, and finally the polylactic acid-glycolic acid copolymer is wrapped by utilizing a neutrophile granulocyte membrane and a stem cell exosome, so that the bionic magnetic nano motor is obtained, and the motor has good biocompatibility. Meanwhile, the motor has an immune escape function and can resist phagocytosis of macrophages in blood. And under the control of an external alternating magnetic field, the medicine can accurately reach a spinal cord injury part, and the effects of inflammation inhibition and neuron recovery can be achieved under the mixed action of neutrophile granulocyte membranes, stem cell exosomes and anti-inflammatory drugs.

This disclosure provides methods and populations of cells, engineered to modulate the expression of select genes and thereby reduce natural killer cell mediated cytotoxicity. For example, this disclosure provides engineered cells equipped with one or more heterologous nucleic acid sequences encoding polypeptides that, when expressed, impede the typical cytotoxicity of natural killer cells as compared to comparable cell devoid of heterologous nucleic acid sequence.

The invention discloses an application of a PHD3 inhibitor in prevention and treatment of AIDS (acquired immune deficiency syndrome). Through multidisciplinary research means of immunology, biochemistry and the like, the situation that virus antisense protein ASP inhibits generation of I-type IFN in the HIV-1 infection process is analyzed, immune escape is achieved, and a latent infection mechanism is established. In the aspect of mechanism, the ASP can play the inhibiting role after transcriptional expression into protein in a body cell through post-translational modification, the 47-site proline of the ASP can be helped to realize the capability of inhibiting the immune response of the body after hydroxylation modification, and the post-translational modification is realized by depending on proline hydroxylase 3 (PHD3) of a host. On the basis of mechanism research, it is found that a PHD3 inhibitor Molidustat counteracts hydroxylation of PHD3 to ASP, so that immune escape of HIV-1 is blocked, infection is antagonized, and good development prospects of AIDS treatment and prevention drugs are shown.

The invention relates to saRNA (Ribonucleic Acid) and application thereof, a saRNA vaccine, a method and a pharmaceutical composition, the saRNA for coding HSV (Herpes Saturation Virus) ICP34.5 is constructed, the translation and expression capability of a gene can be obviously enhanced, the use of the saRNA in a gene delivery system is optimized, a more excellent application carrier is provided for vaccine and gene therapy, the antiviral innate immune response of a host can be inhibited by coding ICP34.5 and saRNA, and the anti-virus innate immune response of the host can be inhibited by coding ICP34.5 and saRNA. According to the present invention, the expression and the translation of the gene are enhanced by inhibiting PKR and IFN signal channels, particularly by inhibiting PKR and IFN signal channels and reducing translation closure, the addition of the ICP34.5 is beneficial to prolonging the expression time of the gene of interest and providing the lasting treatment effect, and the integration of the ICP34.5 ensures the same immune escape characteristic of the offspring saRNA, optimizes the gene delivery system, and improves the efficiency and the effect of the offspring saRNA. By coding ICP34.5 and saRNA, strong innate immune response can be reduced, side effects in gene therapy can be reduced, and a therapeutic window can be improved.

Disclosed are an aggregation-induced emission photosensitizer and a pharmaceutical composition constructed therefrom, a preparation method therefor and the use thereof. The aggregation-induced emission photosensitizer MTCN-3 has a great reactive oxygen species generation capacity and a photothermal effect, thus exerting the dual effect of inducing pyroptosis and ferroptosis in tumor cells. The aggregation-induced emission photosensitizer is also capable of exerting a synergistic photoimmunotherapeutic effect with an immune agonist Poly(I:C). A co-assembled pharmaceutical composition has a near-infrared aggregation-induced emission effect, exhibits good subcellular distribution, and has active targeting selectivity for tumor cells. The pharmaceutical composition eliminates tumors and prevents tumor metastasis by means of inhibiting immune evasion, and inhibits the growth of both primary and distal tumors, thereby exerting a systemic anti-tumor immune effect. The pharmaceutical composition exhibits high stability and low toxic side effects, and has broad prospects for clinical application.

We describe compositions of DNA donor molecules compatible with various gene insertion methods, offering key advantages in delivery, nuclear localization, and immune evasion. The modified DNA donor molecules are predominantly single-stranded but include short regions of double-stranded DNA to reconstruct enzyme binding sites, and can be combined with other methods to enhance donor recruitment to the cell nucleus.

The present disclosure provides methods of treating immune evasive cancers using surface functionalized particles alone or in combination with cancer therapeutics.

The invention belongs to the technical field of biological medicines, and particularly relates to application of NT5M in preparation of a medicine for treating pancreatic cancer. The invention reveals that NT5M is a key metabolic regulatory factor in PAAD and affects tumor progression, immune regulation and drug sensitivity; low NT5M expression is related to poor prognosis, overexpression of the low NT5M inhibits cell migration and invasion and PD-L1 mediated immune escape, the potential of the low NT5M as a tumor inhibition factor in PAAD is highlighted, the low NT5M can be used as a prognosis biomarker and a potential treatment target, and a new treatment strategy can be provided for PAAD patients.

Provided herein are compositions for the prevention and treatment of genital herpes, comprising antigen binding agents to herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, ribonucleic acids (RNAs) encoding these antigen binding agents, and methods of use thereof.

The invention discloses a multispecific anti-gp120 artificial antibody as well as a preparation method and application thereof. The multispecific anti-gp120 artificial antibody is prepared from gold nanoparticles and polypeptide, the two ends of the polypeptide are fixedly connected to the surfaces of the gold nanoparticles through Au-S bonds. According to the invention, the SPR (Surface Plasmon Resonance) technology is utilized to prove that the multispecific anti-gp120 artificial antibody has strong binding force and high affinity to gp120. The cost of the novel multispecific anti-gp120 artificial antibody is the same as that of a single monospecific gold antibody, but the affinity of the novel multispecific anti-gp120 artificial antibody with gp120 is higher, and the novel multispecific anti-gp120 artificial antibody is expected to effectively neutralize various gp120 mutants and inhibit immune escape of HIV viruses. Gp120 of HIV can be prevented from being combined with host cells CD4, and the application prospect in the aspect of HIV prevention and treatment is achieved.

The present disclosure provides a combination comprising ribonucleotide sequences that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion and related methods of treating, suppressing, inhibiting, or preventing an HSV infection. The present disclosure further provides a related formulation comprising ribonucleotide sequences that encode HSV glycoproteins, wherein one or more of the ribonucleotides are fully or partially encapsulated within a lipid nanoparticle, wherein the lipid nanoparticle comprises (a) a polymer-conjugated lipid; (b) a cationic lipid; and (c) one or more neutral lipids. Finally, the present disclosure provides methods of inducing an HSV glycoprotein-specific B-cell response in a subject comprising administering to the subject a composition comprising the HSV glycoprotein.

The present disclosure relates to expressing one or more reprogramming factors utilizing translational enhancing elements in the 5′ and / or 3′ untranslated region (UTR) of synthetic mRNA. The 5′ UTRs include a mini-enhancer sequence and a Kozak sequence whereas 3′ UTR includes a spacer, a stem loop structure, and optionally, a polyadenine tail. The artificial 5′ and 3′ UTRs drive reprogramming factor expression, and in certain examples, do not include modified nucleosides, microRNA sites, or immune-evading factors.

The invention relates to compositions including polynucleotides encoding polypeptides which have been chemically modified by replacing the uridines with 1-methyl-pseudouridine to improve one or more of the stability and / or clearance in tissues, receptor uptake and / or kinetics, cellular access by the compositions, engagement with translational machinery, mRNA half-life, translation efficiency, immune evasion, protein production capacity, secretion efficiency, accessibility to circulation, protein half-life and / or modulation of a cell's status, function, and / or activity.

Provided herein, in some aspects, are methods for using the receptor-binidng domain (RBD) of the SARS-COV-2 S protein, including the the RBD-1, RBD-2, and / or RBD-3 regions, to identify therapeutics for the treatment of SARS-COV-2, developing a vaccine for the treatment or prevention of SARS-COV-2, and identifying a patient as being in need for a treatment for SARS-COV-2.

The present disclosure provides a preparation method of a non-natural anti-human CD45RA murine chimeric antigen receptor (CAR). In the present disclosure, eukaryotic expression vectors pcDNA3.1 / Mu3A4-4-1BB-3ζ and pcDNA3.1 / Mu3A4-4-1BB-3ζ-EGFP and a lentiviral expression vector pLenti / Mu3A4-4-1BB-3ζ are constructed based on molecular biology using a mouse-derived 3A4 antibody. The lentiviral expression vector pLenti / Mu3A4-4-1BB-3ζ can successfully infect human T cells and effectively kill 3A4-positive target cells such as KG1a cells and Raji cells. The recognition of antigens by Mu3A4CAR does not depend on antigen presentation process and is not restricted by a major histocompatibility complex (MHC), thus overcoming tumor immune evasion to kill 3A4-positive tumor cells more effectively.

The application discloses application of a PHD3 inhibitor in prevention and treatment of AIDS. Through immunological, biochemical and other multidisciplinary research means, the application analyzes the mechanism that a viral antisense protein ASP inhibits production of type I IFN to realize immune escape and establish latent infection in an HIV-1 infection process. Mechanically, after being expressed into a protein in a cell in the body, the ASP needs to undergo post-translational modification to exert its inhibiting effect, and after hydroxylation modification of a 47-position proline, the ASP can help to realize the ability of inhibiting the body immune response, and the post-translational modification depends on a host proline hydroxylase 3 (PHD3) to realize. Based on the mechanism-based research, it is found that a PHD3 inhibitor Molidustat offsets the hydroxylation of the ASP by PHD3, thereby blocking the immune evasion of HIV-1 and antagonizing infection, and showing a good development prospect of an AIDS treatment and prevention drug.

This disclosure provides methods and populations of cells, engineered to modulate the expression of select genes and thereby reduce natural killer cell mediated cytotoxicity. For example, this disclosure provides engineered cells equipped with one or more heterologous nucleic acid sequences encoding polypeptides that, when expressed, impede the typical cytotoxicity of natural killer cells as compared to comparable cell devoid of heterologous nucleic acid sequence.

The present disclosure is directed to the identification and use of lipids involved in auto-immune reactions and foreign body responses. A. set of phospholipids was observed to preferentially deposit on immune-evasive implants, and these phospholipids upregulated RNA transcripts of anti-inflammatory proteins in murine macrophages. Additionally, a set of fatty acid lipids was observed to preferentially deposit on immunogenic implants, and these fatty acid lipids upregulated RNA transcripts of inflammatory proteins in murine macrophages. Using selected lipids, implantable devices can be engineered to avoid or to attract host immune responses, thereby regulating the length of time the devices are maintained in vivo.

Prophylaxis, immune boosting and therapy for vascular complications of diabetes employing various formulations of sulfonic polymers to target and control the activation loop of complement system at C3 level. The molecular targets identified and successfully inhibited are Factor B, Factor D, Factor H. First, this contributes to the inhibition of cross talk pathways in classical and lectin system pathways as well as the C3a and C5a interactions with their receptors. The cross talk pathways inhibit inflammation, oxidative stress, fatty acid synthesis and fibrosis. Secondly, it further inhibits downstream pathways of C5b-9 and also coagulation and thrombotic cascade. Both pathways cause micro vascular and macro vascular complications of diabetes. Thirdly, patient safety is enhanced by Double inhibition of Factor H and Factor D. This reduces adverse effects mediated by individual inhibition of Factor H and Factor D and in addition it has immune boosting effect by targeting immune evasion.

The invention belongs to the field of biological engineering and biological treatment, and discloses a CD158d molecule, a neutralizing antibody thereof and application. The invention finds that HS3ST3B1 positive tumor-associated fibroblasts can mediate killing lymphocyte death, and further finds a new immune checkpoint molecule CD158d. As the CD158d molecule can mediate tumor fibroblast mediated killer lymphocyte death, the neutralizing antibody capable of neutralizing the CD158d molecule is obtained in the invention. On the basis, the invention develops an application of the CD158d molecule as a target spot in screening or preparing a medicine for inhibiting tumor immune escape, and an application of the CD158d neutralizing antibody in preparing a medicine for inhibiting tumor immune escape.

Invasive fungal disease (IFD) constitutes an increasing health concern due to growing numbers of patients at risk for opportunistic fungal infections. Among the fungi capable of inducing opportunistic infections the yeast Candida albicans is clinically the most important. Immune evasion proteins like the pH-regulated antigen 1 (Pra1) and the translation elongation factor 1 (Tef1), which are expressed on the fungal surface and are also secreted, are major drivers of pathogenicity. Therefore, novel monoclonal antibodies (mAb) binding these proteins have been developed. In an in vivo mouse model of high-dose septic C. albicans infection, therapeutic application of mAb against Pra1 reduced clinical symptoms of the disease. Prophylactically, mAb against Tef1 protected mice from clinical disease and prolonged survival. The mABs of the present invention may also be efficacious in patients at risk or with already established IFD.