42 results about "Low 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.

Provided is the development and use of a novel immunomodulator. The immunomodulator is an antibody or an antigen-binding portion thereof that binds to CCR8. The antibody has a neutralizing activity in blocking CCL1 / CCR8 axis, can inhibit CCL1-induced cell activation, and for low-affinity FcγRIIIA158F allele carriers in the population, enhances the ADCC effect by means of Fc optimization.

The invention belongs to the technical field of nuclear medicine, and relates to a CAIX-targeted cyclic peptide and a preparation method and application thereof, the CAIX-targeted cyclic peptide structure is shown as a formula 1, Linker is a cyclization connexon, and Chenator is a nuclide chelating group. The CAIX-targeted cyclic peptide provided by the invention has high affinity with CAIX, and has low affinity with isoenzyme CAII of CAIX, so that the CAIX-targeted cyclic peptide has high selective affinity with CAIX; the nuclide-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, and has extremely high tumor uptake, tumor-muscle ratio and tumor-kidney ratio which can meet diagnosis requirements; due to the long-time retention characteristic in tumors, the polymer has a relatively high tumor treatment 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 belongs to the technical field of pharmaceutical chemicals, and provides a dopamine D3 receptor radioactive tracer and a preparation method and application thereof. According to the dopamine D3 receptor radiotracer (11C-YQA14) disclosed by the invention, a structure as shown in a formula 1 is used as a precursor compound, and gaseous 11C-CH3I is introduced under a closed condition to obtain the 11C-YQA14. The dopamine D3 receptor radioactive tracer has ideal affinity to a dopamine D3 receptor and has low affinity to a dopamine D2 receptor, so that the dopamine D3 receptor radioactive tracer can selectively recognize the dopamine D3 receptor and has low recognizability to the dopamine D2 receptor.

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.

The present invention provides a tight junction protein antibody G4 and its application. The antibody G4 is a single-domain antibody, and the heavy chain variable region of the single-domain antibody includes CDR1, CDR2, and CDR3. The amino acid sequence of CDR1 includes SEQ ID NO.1; the amino acid sequence of CDR2 includes SEQ ID NO.2; the amino acid sequence of CDR3 includes SEQ ID NO.3. The tight junction protein antibody G4 obtained in the present invention has a higher affinity for CLDN6 and a lower affinity for CLDN9, that is, it has higher specificity for CLDN6. At the same time, the tumor killing effects mediated by ADCC and CAR-T are better, and the chimeric antigen receptor molecule constructed based on it can better mediate the killing of tumors by immune cells.

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.

This invention provides an antibody combination for detecting tumor necrosis factor-α (TNF-α), comprising a first antibody and / or a second antibody, each possessing a unique CDR fragment. Specific applications of this antibody combination are also provided. The advantages of this invention are that the antibody combination exhibits strong affinity for TNF-α antigen, high detection sensitivity, ease of use, and rapid and stable detection. The concentration of TNF-α in normal human serum is 9.42 ± 2.91 ng / mL. Existing conventional low-affinity antibodies are insufficient for effective detection in this situation. However, the high-affinity antibody combination and the TNF-α quantitative detection kit containing this antibody combination using a double-antibody sandwich method provided by this invention can effectively achieve the quantitative detection of ultra-low concentrations of TNF-α. Verification shows that the kit's sensitivity can reach 2.2 pg / mL.

This invention proposes an immunomicrofluidic chip and its application that can broaden the quantitative analysis range of β-hCG. It includes a substrate and a cover plate pressed onto the substrate, with the substrate and cover plate forming a microchannel. The microchannel is provided with a labeling region and a detection region. The labeling region includes a first labeling region on the lower surface of the cover plate and a second labeling region on the upper surface of the substrate. The detection region includes a low-concentration β-hCG detection region on the lower surface of the cover plate and a high-concentration β-hCG detection region on the upper surface of the substrate. The first labeling region is coated with a labeled anti-human β-hCG antibody, and the second labeling region is coated with a labeled anti-human β-hCG antibody. The low-concentration β-hCG detection region is coated with a high-affinity anti-human β-hCG antibody, and the high-concentration β-hCG detection region is coated with a low-affinity anti-human β-hCG antibody. This enables accurate quantification of β-hCG with a wide concentration range.

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.

The invention relates to the field of protein engineering, in particular to a T cell receptor engineering transformation method and application thereof. The T cell receptor engineering transformation method provided by the invention comprises the following steps: obtaining a CDR region of a given T cell receptor sequence through a database, mutating one or more amino acid residues in the CDR region into histidine, and establishing a first T cell receptor mutation library; the T cell receptor engineering transformation method is based on a histidine scanning method, TCR engineering transformation independent of a three-dimensional structure is achieved, the defect of high affinity is overcome, low-affinity and high-activation TCR transformation is achieved, and more choices are provided for clinical application.

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 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.

The present invention provides antibodies that bind to CD3 with weak or no detectable binding affinity and methods of using the same. According to certain embodiments, the antibodies of the invention bind human CD3 with low affinity and induce human T cell proliferation and hence induce T cell-mediated killing of tumor cells with high efficacy. According to certain embodiments, the present invention provides bispecific antigen-binding molecules comprising a first antigen-binding domain that specifically binds human CD3 with weak or no detectable binding affinity in an in vitro assay, and a second antigen-binding molecule that specifically binds human tumor-associated antigen. In certain embodiments, the bispecific antigen-binding molecules of the present invention are capable of inhibiting the growth of tumors expressing target antigen, such as PSMA. The antibodies and bispecific antigen-binding molecules of the invention are useful for the treatment of diseases and disorders in which an upregulated or induced targeted immune response is desired and / or therapeutically beneficial. For antibodies of the invention are useful for the treatment of various cancers or other diseases where immunotherapy, including effector cell immunomodulation, is warranted.

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 application discloses an antigen-specific T cell in-situ detection method and application, wherein pMHC monomers (peptide-MHC complexes) are nano-spatially organized on a DNA origami scaffold, the valence of pMHC is significantly improved, and stable combination with low-affinity T cells in a tissue slice is realized. Meanwhile, the precise addressing ability of the DNA origami and the design of a signal capture chain are utilized, and the amplification efficiency of a detection signal is greatly improved. In addition, a primer exchange reaction (PER reaction) is utilized to generate a single-stranded DNA product with repeated primer sequences (primer 1 and primer 2), a dendritic structure is formed on the DNA origami scaffold to combine multiple fluorescent groups, and antibody-independent high-fluorescence-intensity in-situ detection is realized, so that the experimental process is simplified and the detection cost is reduced.

This invention provides an antibody combination for detecting transforming growth factor-β1 (TGF-β1), comprising a first antibody and / or a second antibody, each possessing a unique CDR fragment. Specific applications of this antibody combination are also provided. The advantages of this invention are that the antibody combination exhibits strong affinity for TGF-β1 antigen, high detection sensitivity, ease of use, and rapid and stable detection. The concentration of TGF-β1 in normal human serum is 28.4 ± 9.3 pg / ml. Existing conventional low-affinity antibodies are insufficient for effective detection in this situation. However, the high-affinity antibody combination and the TGF-β1 quantitative detection kit containing this antibody combination using a double-antibody sandwich method provided by this invention can effectively achieve the quantitative detection of ultra-low concentrations of TGF-β1. Verification shows that the kit's sensitivity can reach 4.9 pg / mL.

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 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.

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.