35 results about "Lower affinity" patented technology

The invention provides an ORM1 and CEA protein antibody, a combination of the ORM1 and CEA protein antibody and an application of the ORM1 and CEA protein antibody in colorectal cancer diagnosis, and aims to effectively solve the problems of low affinity and specificity and poor stability of the existing antibody by optimizing the immunogen sequences of ORM1 and CEA, screening a monoclonal antibody with high affinity and high specificity, screening the optimal ORM1 and CEA antibody and combining the optimal ORM1 and CEA antibody. The kit has a wide detection range, shows an extremely high collaborative diagnosis value during combined detection, remarkably improves the diagnosis efficiency of early colorectal cancer, and has an important clinical application value.

The invention provides a molecular probe targeting EDB-FN as well as a preparation method and application of the molecular probe. The structural formula of the molecular probe targeting EDB-FN is shown in the specification, according to the molecular probe targeting EDB-FN, the probe is based on a cyclic peptide probe with Lys-Glu side chain lactam bridge conformation fixed, the connection mode of a DOTA chelating agent is optimized, and the clinical transformation bottlenecks that an existing probe is poor in stability, low in affinity, insufficient in targeting specificity, poor in diagnosis and treatment integration compatibility and the like are solved. The probe can be used for early diagnosis and molecular imaging research of tumors, and provides a reliable basis for tumor malignancy degree evaluation and treatment effect monitoring.

The application provides application of TFF1, AAT monoclonal antibodies and combinations thereof in colorectal cancer diagnosis, and solves the problems of low affinity and specificity and poor stability of existing antibodies by optimizing the immunogen sequence of TFF1 and AAT, screening high-affinity and high-specificity monoclonal antibodies, screening the optimal TFF1 and AAT antibodies and combining them, the detection range is wider, and the combination detection shows extremely high synergistic diagnostic value, the early colorectal cancer diagnosis efficiency is significantly improved, and the application has important clinical application value.

Polypeptides comprising a FimH lectin domain comprising at least one an amino acid mutation that causes the FimH lectin domain to be in the low affinity conformation for mannose are described. Pharmaceutical compositions which comprise such polypeptides and methods of stimulating an immune response in a subject in need thereof by administration of the polypeptide are further described.

The application provides application of an antibody of IGFBP4 and CCL14 protein and a combination thereof in diagnosis of colorectal cancer, and solves the problems of low affinity and specificity of existing antibodies by optimizing eukaryotic expression process of recombinant IGFBP4 and CCL14 antigens, greatly improving expression and immunogenicity, screening high-affinity and high-specificity monoclonal antibodies, and screening optimal IGFBP4 and CCL14 antibodies. The antibody has a wider detection range, and has extremely high synergistic diagnostic value when combined detection is performed, significantly improves the diagnostic efficiency of early colorectal cancer, and has important clinical application value.

Disclosed are novel weak affinity IL-2 variants and uses thereof, including adoptive cell therapies by enhancing the efficacy and duration of CAR-immune cells in the treatment of cancer.

The invention provides application of TFF1 and AAT monoclonal antibodies and a combination thereof in colorectal cancer diagnosis, by optimizing immunogen sequences of TFF1 and AAT, screening the monoclonal antibodies with high affinity and high specificity, screening out the optimal TFF1 and AAT antibodies and combining the optimal TFF1 and AAT antibodies, the problems of low affinity and specificity and poor stability of the existing antibodies can be effectively solved, and the colorectal cancer diagnosis efficiency is improved. The kit has a wide detection range, shows an extremely high collaborative diagnosis value during combined detection, remarkably improves the diagnosis efficiency of early colorectal cancer, and has an important clinical application value.

The present invention provides antibodies to TFF3 and OSM proteins, their combination, and their application in the diagnosis of colorectal cancer. By optimizing the immunogenic sequences of TFF3 and OSM, phage display technology is used to screen monoclonal antibodies with high affinity and high specificity. Directed mutagenesis and combinatorial library screening are then used to introduce mutations in the CDR regions of the antibodies to screen out the optimal TFF3 and OSM antibodies. This can effectively solve the problems of low affinity and specificity of existing antibodies, extend the detection range, and demonstrate extremely high collaborative diagnostic value in combined detection, significantly improving the diagnostic efficacy of colorectal cancer and having important clinical application value.

Polypeptides comprising a FimH lectin domain comprising at least one an amino acid mutation that causes the FimH lectin domain to be in the low affinity conformation for mannose are described. Pharmaceutical compositions which comprise such polypeptides and methods of stimulating an immune response in a subject in need thereof by administration of the polypeptide are further described.

Provided in the present invention is a T cell receptor engineering modification method, which comprises the steps of: obtaining CDR regions of a given T cell receptor sequence by means of a database, mutating one or more amino acid residues in the CDR regions into histidine, and establishing a first T cell receptor mutation library. The T cell receptor engineering modification method provided by the present invention is based on a histidine scanning method, realizes TCR engineering modification independent of three-dimensional structures, overcomes the disadvantages of high affinity and realizes the modification of TCRs with low affinity and high activation, thereby providing more options for clinical use. The T cell receptor provided by the present invention comprises the following six CDR regions, CDR1α, CDR2α and CDR3α in a TCRα chain, and CDR1β, CDR2β and CDR3β in a TCRβ chain, the amino acid sequences of which are shown as SEQ ID No. 1-6, respectively. In the present invention, engineering modification of a wild-type MAGE-A3 TCR molecule is achieved by means of a catch bond to obtain an efficient and non-toxic TCR targeting MAGE-A3, which is free of toxic and side effects caused by affinity maturation. Moreover, the engineered TCR is applied to TCR-T cell preparation for solid tumor treatment.

The present invention relates to a chimeric nanobody, a single-molecule localization imaging probe and an imaging method. The chimeric nanobody of the present application sequentially comprises the following sequences from the N-terminus to the C-terminus: the NbGFPe nanobody sequence; a linker with a length of 36 amino acids; the Nb2 nanobody sequence; and a C-terminal linker containing cysteine. The chimeric nanobody of the present invention effectively avoids the problems of low affinity of a single antibody and multi-site labeling, and can achieve high-affinity labeling of 1:1. The probe obtained therefrom for DNA-PAINT super-resolution imaging can obtain high-quality images for imaging various fine structures in cells.

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the αL subunit of human lymphocyte function-associated antigen 1 (LFA-1). The invention particularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 μM Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells.

Disclosed herein is a pipeline to identify variable chains (VCR), which encompass T cell receptors (TCRs) and B cell receptors (BCRs), that recognize epitopes in their low affinity using a bioinformatic statistical method with 10× data that encompasses both preprocessing and identification of antigen-specific VCRs. Also disclosed are methods for treating subjects having viral infections or cancer, the methods comprising administering antibodies from B cells transduced with antigen-specific BCRs and / or modified allogenic T cells transduced with antigen-specific TCRs identified through use of the pipeline.

A technique, called the Coupling Assay for T-cell Specificity (CATS), to identify antigen-specific cells using cell lines expressing MHC II molecules with tethered peptides. CATS successfully identified antigen-specific T cells with a low-affinity peptide, while tetramer failed to identify cells with this same peptide. Increasing avidity on artificial antigen presenting cells can overcome low affinity TCR-pMHC interactions, can identify more responding endogenous populations, and may be specific for the MHCII.

This invention discloses a high-affinity chimeric peptide sensor and a ubiquitin detection method and kit, belonging to the field of biodetection technology. To address the problems of low affinity and poor selectivity in existing ubiquitin detection tools, this invention obtains a V1091L mutant of the HDAC6 ZnF fragment through multidimensional mutagenesis, and integrates other ubiquitin-binding domains using AI and computer simulation to construct a chimeric peptide sensor. Its Kd with monoubiquitin is less than 50 nM, and it can specifically bind some free ubiquitin. This invention also provides a detection method based on this sensor, enabling the detection of free ubiquitin and total ubiquitin through direct or competitive assays. It can calculate the amount of conjugated ubiquitin, determine deubiquitinase activity, and screen ubiquitin pathway regulators. A kit incorporating this sensor is also provided. The sensor of this invention exhibits high affinity and high selectivity, and the detection method requires no complex instruments, making it suitable for complex biological samples and high-throughput detection. It can also distinguish intact free ubiquitin in serum, providing a new tool for basic ubiquitin research and clinical detection, and has significant application value.

The present invention discloses a glycosyl gallic acid derivative, the general structural formula of which is shown below: The present invention designs and synthesizes a class of glycosyl-modified gallic acid derivatives with three-branched benzoic acid as a characteristic mother nucleus, wherein two sugar-type molecules, acetylgalactosamine and galactose, are modified with the three-branched benzoic acid as the characteristic mother nucleus. These are modified on the surface of drugs or drug delivery systems, thereby realizing targeted diagnosis and treatment of liver diseases, overcoming the defect of low affinity for targeting cancer cells in the prior art.

The invention provides antibodies of TFF3 and OSM proteins, a combination thereof and an application of the antibodies in colorectal cancer diagnosis, high-affinity and high-specificity monoclonal antibodies are screened through optimization of immunogen sequences of TFF3 and OSM and a phage display technology, then directed mutation and combinatorial library screening are adopted, mutation is introduced into CDR regions of the antibodies, the optimal TFF3 and OSM antibodies are screened out, and the colorectal cancer diagnosis is realized. The antibody can effectively solve the problems of low affinity and specificity of the existing antibody, is wider in detection range, shows extremely high collaborative diagnosis value during combined detection, remarkably improves the diagnosis efficiency of colorectal cancer, and has important clinical application value.

The present application discloses a bispecific antibody targeting B7H7 and CD3 and a use thereof. The bispecific antibody comprises: a first antigen binding region comprising an anti-CD3 antibody and having CD3-binding activity; and a second antigen binding region comprising an anti-B7H7 antibody and having B7H7-binding activity. The bispecific antibody can bind to human and monkey B7H7 with high specificity and high affinity, and bind to human and monkey CD3 with low affinity and high specificity, promoting PBMC-mediated tumor cell killing.

Polypeptides comprising a FimH lectin domain comprising an amino acid mutation that causes the FimH lectin domain to be in the low affinity conformation for mannose are described. Pharmaceutical compositions which comprise such polypeptides and methods of stimulating an immune response in a subject in need thereof by administration of the polypeptide are further described.

The invention discloses a fluorescent probe of phosphatidylinositol-3, 4, 5-triphosphoric acid, a plasmid, a preparation method and application, relates to the technical field of biology, and aims to solve the problems of low affinity, low specificity and low sensitivity of the existing fluorescent probe of phosphatidylinositol-3, 4, 5-triphosphoric acid. According to the fluorescent probe, two sections of PH-TH structural domain coding sequences of human-derived Btk connected by a first connecting peptide are utilized, a key binding structural domain is subjected to series dimerization, the affinity of the key binding structural domain is amplified by multiple times, the specificity and the sensitivity are enhanced, the structural domain coding sequences are screened and simplified, the cytotoxicity is reduced, and the stability of the probe is improved.

This invention discloses a DNA expression enhancer, belonging to the fields of genetic engineering and DNA drug technology. The enhancer is a polypeptide with ribonuclease III activity and low affinity for ribonuclease inhibitors. It also provides a method for increasing the expression level of a target gene on a plasmid DNA eukaryotic expression vector using the enhancer, comprising the steps of: (a) constructing and preparing an enhancer expression plasmid for eukaryotic cells; and (b) co-transfecting host cells with the target gene expression plasmid and the enhancer expression plasmid. The enhancer increases the expression level and duration of the exogenous target gene in the organism and cells. The recombinant polypeptide enhancer provided by this invention can significantly increase the expression level of the exogenous target gene in mammalian cells, increasing the expression level by approximately 4 to 5 times. This technology, when applied to DNA vaccines, can improve antibody production levels, reduce drug dosage and cost, and greatly enhance the therapeutic effect of DNA drugs.

Provided herein are compounds that bind metal ions (e.g., free metal ions or metal ions bound to low affinity ligands) in a sample or subject. Also provided herein are methods of using the compounds for chelating metal ions and for the treatment of diseases associated with abnormal levels of metal ions. Methods of preparing the compounds and pharmaceutical compositions are also provided.

The present disclosure relates to low affinity chimeric antigen receptors (CARs) and CAR-T cells, which provide cytotoxicity against tumors overexpressing the proto-oncogene CEACAM5 and alleviate on-target, off-tumor toxicities. The CAR-T cells of the present disclosure comprise low affinity anti-CEACAM5 scFvs, which facilitate enhanced anti-tumor activity and a reduced rate of tumor relapse.

The application belongs to the technical field of nuclear medicine, and relates to a CAIX-targeting cyclic peptide as well as a preparation method and application thereof. The structure of the CAIX-targeting cyclic peptide is shown as formula 1. The Linker is a ring-forming linker. The Chelator is a radionuclide chelating group. The CAIX-targeting cyclic peptide provided by the application has high affinity with CAIX and low affinity with CAIX isozyme CAII, so that the CAIX-targeting cyclic peptide has high selective affinity with CAIX. The radionuclide-labeled radioactive probe has high labeling rate and excellent in-vitro stability, has excellent pharmacokinetic characteristics in tumor-bearing model mice of human renal clear cell carcinoma, has extremely high tumor uptake, and can meet the diagnosis requirement of tumor muscle ratio and tumor kidney ratio. The long-time retention characteristics of the probe in the tumor also make the probe have high tumor treatment application value.

The invention provides an application of an IGFBP4 and CCL14 protein antibody and a combination thereof in colorectal cancer diagnosis, by optimizing a eukaryotic expression process of recombinant IGFBP4 and CCL14 antigens, the expression quantity and immunogenicity are greatly improved, a monoclonal antibody with high affinity and high specificity is screened, the optimal IGFBP4 and CCL14 antibodies are screened out, and the colorectal cancer diagnosis efficiency is improved. The antibody provided by the invention can effectively solve the problems of low affinity and specificity of the existing antibody, has a wider detection range, shows an extremely high synergistic diagnosis value during combined detection, remarkably improves the diagnosis efficiency of early colorectal cancer, and has an important clinical application value.

The present disclosure relates to low affinity chimeric antigen receptors (CARs) and CAR-T cells, which provide cytotoxicity against tumors overexpressing the proto-oncogene CEACAM5 and alleviate on-target, off-tumor toxicities. The CAR-T cells of the present disclosure comprise low affinity anti-CEACAM5 scFvs, which facilitate enhanced anti-tumor activity and a reduced rate of tumor relapse.

Compositions comprising one or more targeting (or high affinity) radionuclide-antibody conjugates and one or more non-targeting (or low affinity) radionuclide-antibody conjugates and their use in treating solid tumors are disclosed.

Provided are methods for prophylaxis or treatment of inflammatory arthritis or disorders that are associated with glucocorticoid administration. The methods comprise administering an agent that inhibits phosphorylation of Tau. The method can include administration of a glucocorticoid. The methods include treating glucocorticoid-induced osteoporosis (GIO), dexamethasone mediated osteoclastogenesis, and inflammatory arthritis.

The invention relates to an anti-HER2 / CCR4 bispecific antibody and an application thereof, and provides a bispecific antibody which can target an HER2 target spot and a CCR4 target spot at the same time, the bispecific antibody comprises a first antigen binding region, a second antigen binding region and an Fc structural domain, the first antigen binding region has HER2 binding activity, the second antigen binding region has CCR4 binding activity, and the Fc structural domain has Fc binding activity. And the Fc structural domain is an Fc structural domain of a Trastuzumab monoclonal antibody. The bispecific antibody can be combined with HER2 with high specificity and high affinity and can be combined with CCR4 with high specificity and relatively low affinity; effect cells are promoted to kill tumor cells and Treg cells in a tumor microenvironment, exhaustion of peripheral blood Treg cells caused by a CCR4 monoclonal antibody is effectively avoided, and good anti-cancer activity and higher safety are achieved.

The application provides an antibody of ORM1 and CEA protein, a combination thereof and application in diagnosis of colorectal cancer, and solves the problems of low affinity and specificity and poor stability of existing antibodies by optimizing an immunogen sequence of ORM1 and CEA, screening a high-affinity and high-specificity monoclonal antibody, screening optimal ORM1 and CEA antibodies and combining the same. The combination has a wider detection range, exhibits extremely high synergistic diagnostic value in joint detection, significantly improves the diagnostic efficiency of early colorectal cancer, and has important clinical application value.