24 results about "Lower affinity" patented technology

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 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.

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 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 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.

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.

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.

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.

The present invention provides methods for detecting a complex with low affinity, under conditions in which the binding equilibrium of the complex is substantially maintained, and methods for measuring the concentration and / or amount of the complex. The invention also provides methods for evaluating the kinetics of a complex and methods for deciding on a therapeutic method that uses a pharmaceutical agent, based on the concentration and / or amount of the complex determined by the above-mentioned measurement method.

Provided is a bispecific recombinant protein, comprising a high affinity tumor-targeting arm and a low affinity fusion protein blocking the interaction of CD47 with SIRPα. The antibody corresponding to the high affinity tumor-targeting arm does not bind to CD47, and its binding affinity to the target antigen on the tumor cell is at least 6 times as great as the binding affinity of monomer fusion protein homodimer, corresponding to the low affinity fusion protein blocking the interaction of CD47 with SIRPα, to a CD47 on the tumor cell, wherein the low affinity fusion protein blocking the interaction of CD47 with SIRPα comprises a SIRPα extracellular truncation. Also provided are nucleic acid molecules encoding recombinant proteins and the use of the recombinant proteins and nucleic acid molecules in the manufacture of a medicament for treating tumors.

The present invention is directed to anti-Her2 antibodies and fragments thereof, compositions, and uses thereof. The antibodies and fragments thereof bind to Her2-expressing cells in a pH-dependent manner, with low affinity at the physiological pH typical of normal cells and tissues, and with high affinity at the slightly acidic pH characteristic to solid tumors. Furthermore, the antibodies inhibit the growth of tumor spheroids at a level comparable to that of the benchmark anti-Her2 antibody Herceptin at acidic pH, whereas these effects were significantly reduced at physiological pH. This pH selectivity of cellular growth inhibition is maintained upon antibody conjugation to cytotoxic drugs. The invention also includes methods of treating solid tumors, methods of detecting solid tumors, and methods of pH-dependent capturing of the Her-2 ectodomain.

Provided are a bispecific antibody against human HER2 / CCR4 and a use thereof. Provided is a bispecific antibody capable of simultaneously targeting an HER2 target and a CCR4 target. The bispecific antibody comprises a first antigen-binding region, a second antigen-binding region and an Fc domain, wherein the first antigen-binding region has an HER2-binding activity, the second antigen-binding region has a CCR4-binding activity, and the Fc domain is an Fc domain of a trastuzumab monoclonal antibody. The bispecific antibody can bind to HER2 with a high specificity and a high affinity, and bind to CCR4 with a high specificity and a relatively low affinity. The bispecific antibody promotes effector cells to kill tumor cells and Treg cells in the tumor microenvironment, and effectively avoids the depletion of Treg cells in the peripheral blood caused by CCR4 monoclonal antibodies, thereby having a good anti-cancer activity and a higher safety.