62 results about "Immune Cell Activation" patented technology

The invention belongs to the technical field of biological medicine, and relates to a composite polypeptide composition as well as a preparation method and application thereof. According to the technical scheme, pH responsive polymer loaded oligopeptide-1, acetyl heptapeptide-4 and palmitoyl tripeptide-1 are adopted as a core, hyaluronic acid is adopted for wrapping, a hyaluronic acid layer adsorbs palmitoyl tripeptide-8, heptapeptide-6 and decapeptide-4, and the composite polypeptide with a core-shell structure is prepared and used for treating inflammatory skin diseases. In the acute stage of inflammation, the active ingredients on the outer layer quickly inhibit the activation of proinflammatory factors and immune cells and relieve red, swollen and heat pain, and the gel outer layer formed by hyaluronic acid realizes continuous release, prolongs the action time and supplements moisture to the skin; the pH-responsive polymer of the inner layer releases active ingredients at the inflammation part, so that relapse is prevented, and the skin barrier function is repaired. The composition plays a role from multiple dimensions of inflammation regulation, barrier repair, oxidation resistance and the like through a multi-layer structure design and a multi-component synergistic effect.

Recombinant proteins that stimulate an immune response in the presence of naturally inhibitory ligand binding are described. The recombinant proteins include an extracellular domain of an inhibitory immune cell protein and an intracellular domain of a stimulatory immune cell protein connected via a transmembrane domain. The recombinant proteins can be used to stimulate immune cell activation in the fight against cancers and infectious diseases, among other uses.

ROR1-specific antigen-binders, and multispecific antibodies are provided, which contains one or more ROR1-specific antigen-binding sites and at least one antigen-specific binding site for an activation receptor (such as CD3) on an immune cell, wherein various configurations are presented of new VHH-based anti-ROR1 sequences in relation to the antigen-specific binding site for the immune cell activation receptor, as well as to a scaffolding segment forming a constant region of the antibodies. These multispecific antibodies have been demonstrated to bind to ROR1-positive cancer cells, induce immune cell-mediated cytotoxicity against ROR1-positive target cells, and to inhibit growth of tumor size in animals.

The invention discloses an engineered exosome preparation with tumor targeting and specific gripper response release functions as well as a preparation method and application of the engineered exosome preparation. The preparation comprises a myocardial cell exosome, an NK cell biotinylation activation antibody, a tumor disease biotinylation antibody, streptavidin, a tumor fiber matrix FAP targeting peptide and a tumor matrix enzyme response peptide, and anchoring is carried out through an acetamide compound-polyethylene glycol anchor point platform. The engineering bispecific exosome preparation with good tumor targeting and barrier breakthrough ability and immune cell activation effect is prepared, and the preparation breaks a solid tumor compact fiber barrier and increases NK cell infiltration by utilizing the fibrosis treatment ability of the myocardial cell exosome and the capture and targeting effects of an anchor point platform; the natural killer cells are in close contact with tumor cells, the lasting tumor cell killing effect is achieved, and the tumor matrix environment is fundamentally changed.

The present invention relates to tumor-specific immune cell markers and their uses. Specifically, an immune cell marker combination is provided, comprising: (1) an immune cell activation marker, and (2) an immune cell inhibition marker, optionally further comprising (3) an intracellular marker, and / or (4) a tissue-resident memory marker. The marker combination of the present invention can more accurately identify and enrich tumor-specific immune cells, and the enriched cell population has better tumor reactivity and tumor killing function.

TSLP-TRAPs are a novel class of biologics that have been developed to inhibit the activity of TSLP. By binding to TSLP, TSLP-TRAPS effectively block the interaction between TSLP and its receptor, preventing downstream signaling and immune cell activation. This makes TSLP-TRAPs an attractive therapeutic option for a variety of inflammatory and allergic diseases, including asthma, atopic dermatitis, and eosinophilic esophagitis.

A method for predicting an immune cell activation state is provided, comprising: obtaining a plurality of single immune cell images and a plurality of multiple immune cell images, each immune cell object in the plurality of single immune cell images and the plurality of multiple immune cell images being selected from a set of immune cell objects subjected to a same perturbation condition; processing the plurality of single immune cell images by using a first activation state prediction model to obtain a plurality of first activation state prediction values corresponding to the plurality of single immune cell images respectively, which are output by the first activation state prediction model; processing the plurality of multiple immune cell images by using a second activation state prediction model to obtain a plurality of second activation state prediction values corresponding to the plurality of multiple immune cell images respectively, which are output by the second activation state prediction model; and determining an activation state of the set of immune cell objects based on the plurality of first activation state prediction values and the plurality of second activation state prediction values.

Disclosed herein are immune cells (Bisuper Cells, BS-Cells) that have been engineered to express an immune cell activator polypeptide comprising an extracellular marker domain and incorporate the polypeptide into the cell membrane surface. Also disclosed are immune cells engineered to secrete one or more polypeptide effector molecules, and immune cells engineered to express both molecules. Nucleic acid vectors for expressing these molecules in immune cells are disclosed. Also disclosed are bispecific polypeptides that can be used to specifically bind immune cells expressing immune cell activator polypeptides to another cell. Also disclosed are systems comprising both immune cells and various bispecific polypeptides that can bind to different cell surface proteins of the same or different target cells, e.g., that can be used to expand immune cells in vivo and treat various tumors.

Aspects of the present disclosure include a therapeutic immune cell comprising an Antigen Receptor for Immune Cell Activation (i.e. CAR, TCR, or BiTE) and a Reverse Fate Receptor (RFR). The RFR comprises an extracellular Fas receptor domain, a transmembrane domain and an intracellular domain that transmits cytokine signaling.

Provided herein are constitutively active chimeric cytokine receptors (CACCRs). Such CACCRs allow for increased immune cell activation, proliferation, persistence, and / or potency when present on immune cells bearing chimeric antigen receptors (CARs). Also provided are methods of making and using the CACCRs described herein.

The application provides development and application of an anti-OX40 antibody and immune cell activation, and the anti-OX40 antibody or a fragment thereof of the application has strong binding to human OX40 or Rhesus monkey OX40.

The present disclosure pertains to KIR3DL3 inhibitors (e.g., anti-KIR3DL3 antibodies or antigen-binding fragments thereof) and immune cell activating agents and uses thereof, such as to modify immune effector cells.

The present invention relates to the use of an antibody or an immunologically active fragment thereof, which specifically binds to integrin β2, as an immuno-oncology agent. The chimeric and humanized antibodies of the present invention specifically bind to integrin β2, which is a tumor-specific antigen and is expressed on the cell membrane of M2 tumor-associated macrophages, and thus can be used as an antibody therapeutic agent for cancer treatment using a cancer cell death mechanism by immune cell activation, an antibody therapeutic agent for cancer treatment, or a cell therapeutic agent for cancer treatment, and can also be used for cancer diagnosis.

To provide multispecific B7H3 target compounds and methods for using them. [Solution] A multispecific B7H3 target compound and a method of using the same are provided. The multispecific compound includes a bispecific target protein comprising a B7H3 target domain and an immune cell binding domain; and a triplicate target protein comprising a B7H3 target domain, an immune cell binding domain and an immune cell activation domain. The method of use includes a method of inducing NK-mediated cell death, a method of inducing NK expansion in vivo, and a method of treating cancer.

The invention relates to a dual glycan modified probe for enhancing tumor immunotherapy. A dendritic polymer with alkynyl at the tail end of a branch chain is used as a carrier, and the surface of the dendritic polymer is simultaneously modified with galactose, amino, cyan-5 fluorescent dye, phenylboronic acid and methyl 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrate. According to the treatment scheme, the prepared double glycan modified probe is subcutaneously injected into a tumor peripheral area of a tumor-bearing mouse. And the enrichment condition of the probe in a tumor area is monitored by using a fluorescence signal of cyanine 5. The dual glycan modification probe is connected to sialic acid on the surface of a tumor cell by utilizing the specific recognition effect of phenylboronic acid and sialic acid, and the sialic acid is blocked to hinder immune escape of the tumor cell. More probes are combined to the surfaces of tumor cells through ultraviolet light crosslinking of amino and methyl 4-(4-(hydroxymethyl)-2-methoxy-5-nitrophenoxy) butyrate, and a huge amount of galactose is introduced to promote immune cell activation, so that the aim of enhancing tumor immunotherapy is fulfilled.

The invention belongs to the technical field of biological medicine, and particularly relates to a rheumatism immune disease treatment composition combining traditional Chinese medicine active ingredients and immune regulation and application of the rheumatism immune disease treatment composition, and the rheumatism immune disease treatment composition comprises the following components in parts by weight: 10-50 parts of a traditional Chinese medicine active ingredient compound; 0.01 to 1 part of an immune regulation factor; 50 to 90 parts of pharmaceutic adjuvants; wherein the traditional Chinese medicine active component compound is prepared from the following components: astragaloside, artemisinin, curcumin and triptolide in a weight ratio of (2-5): (1-3): (1-4): (0.5-2); the immunoregulation factor is composed of recombinant human interleukin-10 (rhIL-10), a transforming growth factor-beta1 (TGF-beta1) and a CTLA4-Ig fusion protein according to a weight ratio of (1-3): (0.5-2): (1-4). The active ingredients of the traditional Chinese medicine cover a plurality of links of anti-inflammation, anti-oxidation, immunoregulation and the like, and immunoregulatory factors accurately intervene in immune cell activation and a cell factor network to jointly inhibit abnormal immune response.

The invention relates to an application of India giant globular bacteria in preparation of a medicine for regulating a tumor microenvironment, and belongs to the technical field of biological medicines. The invention provides an application of India giant globular bacteria XA-511 in preparation of a medicine for regulating a tumor microenvironment. Researches show that the India giant globular bacteria XA-511 can be colonized in a tumor microenvironment, the tumor microenvironment can be transformed through a metabolic pathway of the India giant globular bacteria XA-511, immune cell activation enhancement and the like, and cold tumors are transformed into hot tumors, so that the treatment effect of the immunosuppressor on tumors is promoted. Furthermore, treatment of secondary tumors is more difficult than primary tumors, since tumors may be present at multiple sites, and the volume and number of tumors may vary over time. And by virtue of the characteristic of a tumor hypoxia environment, the India giant globular bacteria XA-511 can be selectively colonized at a tumor occurrence part after entering a systemic circulatory system, so that the tumor microenvironment is specifically changed, and the treatment effect of the immunosuppressor on tumors is enhanced.

The invention discloses sprayable hydrogel for tumor postoperative adhesion prevention and immunotherapy as well as a preparation method and application of the sprayable hydrogel, and belongs to the technical field of biomedical materials. The sprayable hydrogel comprises a hydrogel matrix material and a nano material dispersed in the hydrogel matrix material; wherein the nano material is an ovalbumin liposome; the hydrogel matrix material is prepared from oxidized konjac glucomannan and methacrylated gelatin. According to the sprayable hydrogel, on a biological tissue interface, one side has stable tissue adhesion capacity, and the other side keeps free from surrounding tissues; due to the asymmetric adhesion design, the unexpected adhesion problem caused by indifference adhesion of traditional hydrogel can be reduced; in addition, drug release is doubly regulated and controlled through liposome and a gel network, antigen burst release is avoided, immune cell activation is remarkably promoted, and then the tumor recurrence rate is remarkably reduced.

The present invention provides the development and application of anti-OX40 antibodies and immune cell activators, and the anti-OX40 antibodies or fragments thereof of the present invention retain relatively strong binding to human OX40 or rhesus monkey OX40.

Disclosed herein, in some aspects, are compositions and methods for enhancing immunosuppressive functions of a cell, polynucleotides encoding polypeptides for effectuating the same, cells comprising the same, and compositions comprising the polypeptides, polynucleotides, and / or cells. In some aspects, the engineered cells show enhanced immunosuppression. Also disclosed are methods for disease treatment, such as graft-versushost disease, sepsis, transplant rejection, and / or autoimmune diseases, comprising administering engineered cells and / or compositions of the disclosure to a subject in need thereof.

The present invention relates to a method of increasing immune cell activation and / or treating cancer in a subject comprising administering to the subject an effective amount of a compound of formula (I): HNOR1ONOR2O # imgabs0 # or a pharmaceutically acceptable salt thereof: HNOR1ONOR2O # imgabs0 #

The invention relates to a humanized antibody of a targeted human hepatic ligand protein A receptor 10 and application thereof, the specific antibody of the hepatic ligand protein A receptor 10 (EphA10) or a fragment with immunocompetence of the antibody is specifically combined with the EphA10, and the EphA10 is a very promising target spot for overcoming the drug resistance and resistance of the existing immune checkpoint inhibition factor targeted therapeutic agent. And when an ADC is prepared using the antibody, it is shown that it is capable of specifically killing cancer cells, and thus it is useful as an antibody therapeutic agent for treating cancer using a mechanism that causes cancer cell death by immune cell activation, an antibody therapeutic agent for treating EphA10-expressing cancer, or a cell therapeutic agent for treating EphA10-expressing cancer, and it is useful as an antibody therapeutic agent for treating EphA10-expressing cancer. And can also be used for cancer diagnosis.

The present disclosure provides high-performance immune-activation reporter cell line set. A set of nucleic acid constructs comprising one or more response elements operatively linked to a TATA box motif promoter or a minimal IL-2 promoter are provided. A set of reporter cell lines comprising a polynucleotide sequence encoding a reporter protein under the control of one or more response elements operatively linked to a TATA box motif promoter or a minimal IL-2 promoter is also provided. The provided set of reporter cells enable sensitive and signal-enhanced bioassay performance to reflect and evaluate adaptive immune cell activation / inhibition regulated by the immune receptors CD3, co-stimulatory CD28 and related signaling pathways, and avoid responding bias triggered by particular transcription factor. A controllable engineer method for a functional cell line is further provided.

The invention belongs to the field of precise diagnosis and treatment, and particularly relates to an immunoconjugation medicine, a medicine composition based on the immunoconjugation medicine and application of the immunoconjugation medicine in the field of tumor treatment. Specifically, the immunoconjugation drug comprises a targeted tumor fragment (TTF) combined with a tumor marker in a targeted manner and a targeted immune cell fragment (ITF) combined with an immune cell surface molecule, the two fragments are connected through a linker fragment (Lk), the tumor cells can be targeted and the immune cells can be connected at the same time, the immune cells do not need to be transfected, and the immunoconjugation drug can be applied to the immunoconjugation drug. The immune cells can be activated, and the capabilities of targeting tumors and killing the tumors are obtained.

Provided is a pseudotyped viral particle, a viral envelope surface thereof comprising immune cell-targeting molecules and / or immune cell-activating molecules. Corresponding targeting molecules are designed on the basis of cell receptors to be targeted, enabling targeting of different types of cells. The application scope is broad, including but not limited to the rapid preparation of CAR-T, CAR-NK, and other immunotherapeutic cells in vitro without the need for sorting and activation, as well as the direct generation of CAR-T, CAR-NK, and other immunotherapeutic cells in vivo.

Disclosed herein, in some aspects, are dual stimulatory receptors (DSRs), polynucleotides encoding the same, immune cells comprising the same, and compositions comprising the polypeptides, polynucleotides, and / or immune cells. In some aspects, DSRs enhance immune cell activation and / or anti-tumor activity. Also disclosed are methods for disease treatment, such as cancer treatment, comprising administering such immune cells and / or compositions to a subject in need thereof.

The invention discloses an in-vitro amplification method of dog peripheral blood source specific immune cells, and belongs to the technical field of immune cell culture. According to the method, dog peripheral blood serves as a cell source, and efficient amplification of specific immune cells is achieved within 14 days through the steps of lymphocyte separation, immune cell activation, staged density regulation and control culture, culture medium supplementing and the like. By optimizing the combination and concentration of cell factors and accurately regulating and controlling the cell density at different culture stages, the problems of low amplification efficiency, weak specific killing ability, short cell activity maintenance time and the like of the dog immune cells in the prior art are solved. The amplification multiple of the finally obtained specific immune cells can reach 125 times or more, the cell viability is kept 90% or more, the proportion of CD3-NKp46 + phenotype cells exceeds 70%, the application requirements of clinical anti-tumor immune cell preparations can be met, and an efficient and stable cell preparation scheme is provided for dog tumor immunotherapy.

The present invention relates to tumor-specific immune cell markers and their uses. Specifically, an immune cell marker combination is provided, including: (1) an immune cell activation marker, and (2) an immune cell inhibition marker, optionally further including (3) an intracellular marker, and / or (4) a tissue-resident memory marker. The marker combination of the present invention can more accurately identify and enrich tumor-specific immune cells, and the enriched cell population has better tumor reactivity and tumor killing function.

The present invention relates to: an antibody specifically binding to GPC3; a CAR-T using same; a humanized antibody of the antibody; and a use of a CAR-T using the humanized antibody. A novel antibody specifically binding to GPC3 protein and a fragment or humanized antibody thereof having immunological activity according to the present invention specifically binds to GPC3, involved in signaling (YAP and Wnt / b-catenin signaling) playing an important role in cancer formation / progression, and exhibits an anticancer immune response, and thus can be used as an antibody therapeutic agent for cancer treatment and as a cell therapeutic agent using cancer cell-killing mechanisms via immune cell activation, and can also be used for cancer diagnosis.

A microfluidic sample preparation device, a fully automated analysis pipeline, a method of conducting an immune cell activation and analytical test.