19 results about "Low 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.

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.

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.

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 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.

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 application relates to a preparation and application of a chimeric antigen receptor targeting BCMA. The immunogenicity of scFv is significantly reduced by humanizing the mouse-derived antibody, and the human anti-mouse antibody (HAMA) reaction can be reduced, and the persistence and safety of CAR-T cells in the patient body can be improved. The affinity (KD approximately 1.46E-07 M) of the preferred scFv (such as D12.u21) obtained by the application to BCMA is reduced by about 10,000 times compared with that of a commercial high-affinity scFv (C11D5.3, KD approximately 1.09E-11 M). The "medium-low" affinity characteristic aims to balance the activation strength of CAR-T cells and avoid T cell exhaustion caused by excessive activation. Although the affinity is greatly reduced, the CAR-T cells expressing the preferred scFv (D12.u21) of the application show better killing effect than the high-affinity control (C11D5) CAR-T cells in in-vitro experiments. Under a higher target ratio, the killing efficiency and IFN-gamma cytokine secretion level of the CAR-T cells are both significantly higher, indicating that the CAR-T cells have stronger effector function and activation potential.

The application discloses a brain-targeting peptide screening method, introduces LSTM, trRosettaX, AlphaFold2, Point Transformer deep learning technology and Autodock Vina molecular docking tool, generates brain-targeting peptide sequences, predicts deep learning peptide structures, docks proteins and peptides and predicts spatial affinity, increases biochemical characteristic information of target points and peptides through Point Transformer deep learning screening, applies double structures of molecular docking combined free energy score and Point Transformer spatial affinity score for screening, and realizes brain-targeting peptide screening. The method can accelerate the screening process of brain-targeting peptides, shorten the experimental period, reduce the screening cost, realize rapid screening, improve the binding accuracy and screening accuracy of peptides and target points, and effectively screen out candidate peptides with low affinity.

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 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.