43 results about "Internalization" patented technology

The present invention relates to the technical field of immune engineering, and in particular to a CD155-targeting antibody or antigen-binding fragment and a use thereof. The antibody comprises a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 23 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 24, or a heavy chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 25 and a light chain variable region having at least 70% identity to a sequence shown in SEQ ID NO: 26. The antibody has an excellent binding capability with CD155, and CAR-T cells constructed on the basis of the antibody have a significant killing capability against tumor cells expressing CD155, as well as an obvious cellular internalization effect, the capability of promoting the cytotoxic effect of NK cells, and the capability of promoting the phagocytosis effect of macrophages, thereby exhibiting an excellent anti-tumor effect.

In the present invention, an antibody or antigen-binding fragment thereof that specifically binds to an extracellular region of the CD179b protein expressed on a cell surface and has the ability to be internalized into cells expressing the CD179b protein on the cell surface can be used as an intracellular drug delivery agent for delivering a drug into cells expressing the CD179b protein on the cell surface.

Disclosed are compositions that can bind to a CCR6 G Protein-Coupled Receptor (GPCR) and to a transferrin receptor on a cell surface. Once bound, the protein of interest (CCR6) can be internalized and / or degraded inside a cell.

Provided herein are isolated anti-LRRC15 antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates (e.g., antibody-drug conjugates), which specifically bind to LRRC15 and are internalized by LRRC15 expressing cells. Also provided are nucleic acids encoding the anti-LRRC15 antibodies and antigen binding portions, methods for treating cancer comprising administration of LRRC15-targeted antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates and / or associated therapies, as well as methods of diagnosis, and kits.

The present application provides a PSMA-targeting ligand compound and chelate thereof and use thereof. The structure of the PSMA-targeting ligand compound is shown in formula I, wherein R1, R2 and R4 are each independently selected from H and optionally substituted C1-C5 linear or branched alkyl; R3 is selected from optionally substituted aryl ring group and optionally substituted aromatic heterocyclic group; X is a sulfur or oxygen atom; Y is selected from a chemical bond and -NH-(CH2)m-, wherein m is an integer selected from 0-18; and Z is a radioactive metal ion chelating group. The pharmacokinetic characteristics of the PSMA-targeting ligand compound are obviously improved, which can be more effectively absorbed by the human body, stably exist in the body, and be taken up and internalized by cancer cells, so that the coupling of the radioactive nuclide can obtain cancer treatment drugs and diagnostic reagents with obviously improved therapeutic effect.

This invention discloses a novel class of peptides for targeted cancer therapy and their corresponding drug or fluorescent dye conjugates, belonging to the field of biomedical technology. These peptides are designed based on the optimized structure of natural LHRH-III, enabling them to specifically bind to and efficiently internalize into tumor cells overexpressing luteinizing hormone-releasing hormone receptor (LHRH-R). After fluorescent conjugation, their targeting ability against 4T1 cells is comparable to that of the classic peptide [D-Lys]. 6 The [-LHRH-I] peptide exhibits comparable to or superior performance and significantly improves cellular internalization efficiency. In vivo distribution studies have shown that its liver accumulation is significantly reduced compared to the control group, effectively lowering the risk of hepatotoxicity. Furthermore, by conjugating the targeting peptide with antitumor drugs (such as camptothecin or doxorubicin) via disulfide linkers, the resulting peptide-drug conjugates (PDCs) demonstrate excellent responsive drug release characteristics and good in vitro and in vivo antitumor activity. The peptides and conjugates provided by this invention have potential application value in cancer targeted therapy and diagnosis with high specificity and low toxicity.

New cell-penetrating peptides including or consisting of an amino acid sequence selected from among the sequences SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8. Further, fusion proteins including the peptides and a molecule of pharmaceutical, diagnostic or biotechnological interest.

This invention relates to mitochondrial-enriched extracellular vesicles, their preparation methods, and applications, which can effectively solve the drug problem in spontaneous intracerebral hemorrhage. The technical solution involves using platelets as raw material, and obtaining platelet-derived extracellular vesicles carrying active mitochondria through activation induction, differential centrifugation and fractionation, membrane filtration and elution enrichment. This achieves efficient and stable loading of functional mitochondria, and the resulting PEV Mito has a complete structure and uniform particle size, which can effectively maintain mitochondrial membrane potential and biological activity. It can achieve efficient delivery and intracellular internalization to damaged neurons and restore mitochondrial function. The PEV Mito prepared by this invention has high delivery efficiency and excellent biocompatibility, and can be used to prepare drugs for the treatment of intracerebral hemorrhage and secondary neurological injury, with good prospects for clinical translation.

This invention discloses a metal-nucleic acid coordination nanosystem, its preparation method, and its application. The preparation process of the nanosystem is as follows: CuCl2 solution, MnCl2 solution, siRNA solution, and EGCG solution are mixed and reacted at 37°C with stirring to obtain preliminary nanoparticles, denoted as Cu-Mn-siRNA; the obtained Cu-Mn-siRNA nanoparticles are mixed with PEI solution and co-incubated for surface coating. After purification, the final target nanomaterial is obtained, denoted as Cu-Mn-siRNA@PEI. After entering tumor cells, the surface-modified PEI enhances the interaction between the nanoparticles and the negatively charged cell membrane through its positive charge, thereby promoting the internalization and uptake of the nanosystem by the cells. Under the high GSH environment within the cells, the coordination structure dissociates, releasing Cu... 2+ Mn 2+ And siGPX4. This nanosystem integrates the catalytic function of bimetallic ions, the gene silencing function of siRNA, the coordination-assisted function of EGCG, and the delivery and stabilization function of PEI, achieving synergistic therapy of "reactive oxygen species generation + target gene silencing".

The antibodies of the present invention have specific binding activity to HLA-DQ2.5 and may have binding activity to HLA-DQ2.2 and / or HLA-DQ7.5, but substantially no binding activity to HLA-DQ8, HLA-DQ5.1, HLA-DQ6.3, HLA-DQ7.3, HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5. The antibodies bind to HLA-DQ2.5 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5 and TCR, and thus block the interaction between HLA-DQ2.5 and an HLA-DQ2.5-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain.

The application belongs to the technical field of biotechnology and medicine, and specifically discloses a single-domain antibody-exosome compound (Nb-EMX2-Exos) targeting EMX2 as well as a preparation method and application thereof. The compound is prepared by covalently coupling a single-domain antibody (Nb-EMX2) specifically binding to EMX2 protein to the surface of endometrial stem cell-derived exosomes (ESC-Exos). In-vitro experiments show that the compound can specifically recognize and efficiently internalize into damaged endometrial stromal cells with high expression of EMX2, and significantly promote the migration and proliferation of the cells. In-vivo experiments further prove that the compound can precisely target and enrich in damaged endometrial tissue, effectively promote the structural repair (thicken the endometrium and reduce fibrosis) of the endometrium, and completely restore the fertility function. The application provides a novel targeted treatment preparation for solving the problems of poor targeting of natural exosomes and limited treatment effect, and has important application value in the treatment of endometrial injury repair and related infertility.

Bispecific antibody against EGFR and c-Met. The heterodimeric interaction between the EGFR binding arm and the c-Met binding arm of the bispecific antibody is stronger than the interaction of each in the source homodimer by modifying the Fc segment amino acid sequence of the binding arm, so that it can be assembled into a heterodimer in vitro; its effect on inhibiting the proliferation of EGFR and c-Met double-positive tumor cells is stronger than the combination of EGFR monoclonal antibody and c-Met monoclonal antibody, mediates antibody-dependent cellular cytotoxicity (ADCC), promotes target protein internalization and inhibits the proliferation of osimertinib acquired resistant cell lines. Since the prepared bispecific antibody is simple to prepare, stable in structure, and can obtain a pure bispecific antibody by in vitro assembly, it is expected to better meet the clinical treatment needs, and therefore has a good market prospect.

This disclosure provides cell penetrants comprising a cell internalization module and an antibody or antigen-binding antibody fragment thereof that specifically binds to human β-amyloid, and methods of using these cell penetrants to treat patients with β-amyloid-related diseases, including inclusion body myositis (IBM).

This invention relates to the application of mitochondrial formulations in the preparation of drugs for treating chronic obstructive pulmonary disease (COPD). The mitochondrial formulations contain active mitochondria isolated from healthy donor cells, with a particle size of 400–1000 nm, possessing normal mitochondrial membrane potential and ATP generation function, and capable of being internalized by mammalian COPD lung epithelial cells. In vitro cell experiments have confirmed that this mitochondrial formulation can repair CSE-induced mitochondrial dysfunction in lung epithelial cells, inhibit mPTP opening, reduce mtDNA leakage into the cytoplasm, thereby blocking the activation of the cGAS-STING signaling pathway and reducing the release of inflammatory factors such as IL-1β and TNF-α. In vivo experiments in COPD mouse models show that tail vein injection of the mitochondrial formulation can effectively accumulate in lung tissue, significantly improving lung pathological changes such as emphysema and collagen fiber deposition in model mice. This invention provides a novel strategy for COPD treatment based on repairing mitochondrial function and intervening in inflammatory signaling pathways.

Provided herein are isolated anti-LRRC15 antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates (e.g., antibody-drug conjugates), which specifically bind to LRRC15 and are internalized by LRRC15 expressing cells. Also provided are nucleic acids encoding the anti-LRRC15 antibodies and antigen binding portions, methods for treating cancer comprising administration of LRRC15-targeted antibodies, antigen binding portions thereof, bispecific antibodies, and conjugates and / or associated therapies, as well as methods of diagnosis, and kits.

A genetically modified Salmonella cell (GMSC) engineered to exhibit specific targeting to cells and regulated delayed lysis in vivo, the GMSC comprising a first heterologous nucleic acid that encodes a first gene product that causes the GMSC to be selectively localized to and / or internalized by a target cell in vivo and a second heterologous nucleic acid that encodes a second gene product that facilitates killing of the target cells following internalization.

The present disclosure provides a method for degrading a target protein, comprising: contacting an IL-2Rβγ positive cell with a multispecific binding protein, wherein the multispecific binding protein comprises: a) a first cell surface binding moiety that specifically binds to a CD122 (IL-2Rβ) subunit and / or a CD132 (IL-2Rγ) subunit, on the surface of the IL-2Rβγ positive cell, wherein the first cell surface binding moiety comprises at least one immunoglobulin domain or a fragment thereof; and b) a second binding moiety that is operatively linked to the first cell surface binding moiety and that specifically binds to the target protein, wherein specific binding of the multispecific binding protein to the IL-2Rβ subunit and / or the IL-2Rγ subunit facilitates the internalization of the target protein into the IL-2Rβγ positive cell. The present disclosure also provides multispecific binding proteins and methods of using the multispecific binding proteins to treat disease.

This document provides compositions and methods for modulating the internalization properties of cell surface molecules, such as converting non-internalized cell surface antigens into internalized cell surface antigens and converting internalized cell surface antigens into non-internalized cell surface antigens. In some embodiments, engineered antibodies are provided, each comprising an antigen-binding moiety specific to a guide antigen and another antigen-binding moiety specific to an effector antigen, wherein the internalization properties of said engineered antibody or a functional fragment thereof are determined by the relative surface density ratio of said guide antigen to said effector antigen. Recombinant cells, recombinant nucleic acids encoding such engineered antibodies, and pharmaceutical compositions containing them are also provided. This disclosure also provides methods for modulating cell internalization in cells or subjects, and methods for modulating cell type-selective signaling in subjects and / or for treating diseases.

The present application relates to the technical field of biological materials, and particularly relates to in-situ programmed synthesis of quantum dots of cells and a preparation method and application thereof. The core innovation of the present application is that a multi-level nano-synthesizer with responsiveness is designed, and a bottleneck that functional nano-materials cannot be in-situ synthesized at the level of living bodies and cells is broken. The present application promotes the development of biological synthesis of nano-materials, especially in-situ programmed synthesis of quantum dots. After the unique nano-synthesizer of the present application is internalized by cells, a diselenide bond is cleaved by glutathione to generate active selenium species, then the silicon shell skeleton collapses, silver precursors are released, and quantum dots are generated by reaction with selenium precursors. The quantum dots provided by the present application can be in-situ synthesized at tumor sites, induce oxidative stress, combine with the photothermal effect of near-infrared quantum dots, and finally lead to tumor cell apoptosis or necrosis, effectively delaying the development of tumors in tumor-bearing mice and prolonging the survival period of the mice.

This invention provides a bispecific antibody targeting tissue factors, an antibody-drug conjugate (ADC), its preparation method, and its application, belonging to the field of biopharmaceutical preparation technology. The bispecific antibody provided by this invention can efficiently target tissue factors in tumor cells, exhibiting advantages such as strong affinity and high endocytosis efficiency. This invention also provides an ADC, which, under the action of the bispecific antibody, specifically binds to tumor surface antigens and is internalized into tumor cells, achieving precise drug delivery for antitumor drugs. The ADC provided by this invention exhibits good tumor-suppressing effects in both cell and animal models, and is non-toxic and harmless to animals, demonstrating excellent potential for cancer treatment.

The invention relates to novel cell-penetrating peptides comprising or consisting of an amino acid sequence selected from the sequences SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, and SEQ ID NO: 8. The invention further relates to fusion proteins comprising said peptides and a molecule of pharmaceutical, diagnostic, or biotechnological interest. Figure for the abstract: Fig. 1

The application discloses a use of hyperoside in resisting equid herpesvirus 8 (EHV-8) infection. Through qPCR, Western Blot and other experimental techniques, it is revealed on multiple levels that the hyperoside can significantly inhibit the replication of EHV-8, and the mechanism of the hyperoside in resisting the EHV-8 infection is clarified from the aspect of blocking the internalization of the EHV-8, so that the hyperoside can be applied in preparing an anti-EHV-8 medicine.

This invention relates to a unit drug conjugate wherein a binding group capable of binding to another drug conjugate is further linked to a unit drug conjugate in which a target substance and a drug specifically binding to a target cell are linked together. When the unit drug conjugate according to the invention is administered sequentially in vivo, the complex forms clusters through in vivo cross-linking, and these clusters promote endocytosis of the drug conjugate, thereby significantly enhancing the cellular internalization of the drug contained in the drug conjugate.

The present invention addresses the problem of providing a novel therapeutic agent for treating patients with anti NMDAR encephalitis. Patients with an anti NMDAR encephalitis have a pathogenic anti-human NR1 antibody that induces internalization of NMDAR on cell surface. As a result, NMDAR function is weakened in the patients' brain. The present inventors found that the one-armed anti-human NR1 antibody according to the present invention binds to NR1 competitively with the pathogenic anti-human NR1 antibody and inhibits the internalization of NMDAR by the pathogenic anti-human NR1 antibody to thereby exhibit therapeutic effect on anti NMDAR encephalitis. Accordingly, the present invention provides the a one-armed anti-human NR1 antibody, a polynucleotide encoding the antibody, an expression vector containing the polynucleotide, a host cell transformed by the expression vector, a method for producing the antibody, a pharmaceutical composition comprising the antibody, a use of the antibody in the manufacture of the pharmaceutical composition, and a method for treating anti NMDAR encephalitis using the antibody.

Provided are an anti-MUC1 antibody or an antigen-binding fragment thereof, and the use thereof. The MUC1 antibody or the antigen-binding fragment thereof comprises a heavy chain variable region VH and a light chain variable region VL, wherein the heavy chain variable region VH comprises HCDRHCDR2 and HCDR3, and the light chain variable region VL comprises LCDR1, LCDR2 and LCDR3. The antibody exhibits good affinity for a tumor-specific MUC1 antigen, and has significant internalization ability toward cells expressing MUC1.

Provided are an antibody or an antigen-binding fragment thereof that binds to CDH6 and has internalization activity, a derivative comprising the antibody or the antigen-binding fragment thereof, and an antibody-drug conjugate. Also disclosed is a related use of the antibody or the antigen-binding fragment thereof in the treatment, detection and diagnosis of CDH6-related diseases.

The present invention relates to: a composition containing a conjugate having a bioactive polypeptide linked to an immunoglobulin Fc fragment, wherein the composition is a sustained pharmaceutical composition containing a monomer conjugate having one molecule of bioactive polypeptide linked to one immunoglobulin Fc fragment, and optionally a multimer conjugate having two or more molecules of identical bioactive polypeptide linked to one immunoglobulin Fc fragment, wherein the molar ratio of the monomer conjugate to the multimer conjugate in the composition is 19 or greater; a bioactive polypeptide monomer-immunoglobulin Fc fragment conjugate in which a bioactive polypeptide monomer and an immunoglobulin Fc fragment are linked via a non-peptide linker, wherein the bioactive polypeptide is linked, in a monomer form, to one immunoglobulin Fc fragment via the non-peptide linker, and demonstrates a lower receptor-mediated internalization or receptor-mediated clearance, compared to a dimer conjugate having two molecules of bioactive polypeptide linked to one immunoglobulin Fc fragment via a non-peptide polymer, or a bioactive polypeptide- immunoglobulin Fc fragment inframe conjugate; and a method for preparing the sustained pharmaceutical composition.

Provided herein are conjugates comprising a promoter peptide conjugated to an agent, such an antibody or antigen-binding fragment thereof. The promoter peptides promote the cellular internalization of the agent (e.g., the antibody or antigen-binding fragment thereof). The promoter peptides, when conjugated to an agent that binds a target protein (e.g., a receptor), can also promote internalization of the target protein into a cell. Also provided are methods of using the conjugates provided herein, e.g., for promoting the uptake of an antibody or antigen-binding fragment thereof into a cell, for promoting the uptake of a target protein into a cell.