14 results about "B-cell affinity maturation" patented technology

The invention relates to the technical field of biology, in particular to a method for improving affinity of a nano antibody based on computer-aided design. According to the method, a series of bioinformatics tools for nano antibody affinity maturation are investigated and researched in literatures, and part of databases, servers and software are optimized to construct a set of computer-aided design (CAD) nano antibody affinity improvement method by evaluating the operability and the improvement effect of the tools. In order to verify the effectiveness and universality of the method, based on the method, a high-affinity mutant nano antibody is virtually screened out of an Anti-Nectin-4 camel source nano antibody NBNT-1 and an Anti-PD-L1 shark source nano antibody NBNT4 screened in a synthetic library through model construction, model evaluation, site prediction, molecular docking, structural analysis, mutation prediction and mutation evaluation. Traditional in-vitro affinity maturation methods, such as error-prone PCR, are low in screening efficiency, large in randomness introduced by mutation, long in experimental period, large in workload and difficult to accurately optimize the affinity of target molecules. According to the method, various defects of a traditional in-vitro affinity maturation method are overcome, and the success rate and efficiency of affinity maturation are improved.

The application discloses an anti-human PD1 full human antibody and application thereof, and relates to the field of antibodies, and specifically discloses an anti-human PD1 full human antibody, which comprises three heavy chain variable regions HCDR and three light chain variable regions LCDR; the three heavy chain variable regions comprise: HCDR1 is an amino acid sequence as shown in SEQ ID NO. 4, HCDR2 is an amino acid sequence as shown in SEQ ID NO. 5, and HCDR3 is an amino acid sequence as shown in SEQ ID NO. 6; and the three light chain variable regions comprise: LCDR1 is an amino acid sequence as shown in SEQ ID NO. 1, LCDR2 is an amino acid sequence as shown in SEQ ID NO. 2, and LCDR3 is an amino acid sequence as shown in SEQ ID NO. 3. The application has reduced immunogenicity, and affinity maturation and activity are greatly improved.

This invention discloses an APLN monoclonal antibody, its preparation method, and its applications. The APLN monoclonal antibody includes a light chain variable region and a heavy chain variable region. The amino acid sequence of the light chain variable region is shown in SEQ ID No:1, and the amino acid sequence of the heavy chain variable region is shown in SEQ ID No:2. The APLN monoclonal antibody is obtained by immunizing mice with APLN protein, followed by single-cell B-cell sorting and single-cell PCR. Utilizing advanced single-cell B-cell cloning technology combined with single-cell PCR, a novel APLN monoclonal antibody has been developed. The obtained antibody sequence is the result of natural affinity maturation screening by the in vivo immune system, requiring no additional humanization or in vitro affinity maturation steps. It retains the natural high affinity and specificity, and can directly obtain all-natural antibodies with high affinity and high specificity.

OF THE INVENTION Provided herein is a humanized J3 derivative antigen binding molecule and uses thereof.

Using rabbit antibody technology, an anti-TfR1 monoclonal antibody having high affinity, high specificity and high blood safety is obtained by means of phage immune library construction and screening, and the anti-TfR1 monoclonal antibody is subjected to humanization and affinity maturation treatment to obtain a humanized anti-TfR1 monoclonal antibody having high affinity without inducing immunogenicity.

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 application discloses a nanobody Nb3-P-3 capable of specifically recognizing fludioxonil and an application thereof. An amino acid sequence of the nanobody Nb3-P-3 is shown as SEQ ID No. 1. An AI-guided affinity maturation strategy is adopted to perform multi-point synergistic mutation and computer-aided screening on a key binding site of an initial nanobody Nb3, so as to obtain the nanobody Nb3-P-3. The nanobody can specifically recognize fludioxonil, a half-inhibitory concentration (IC 50 ) of the nanobody for fludioxonil is 1.95 ng / mL, a lowest detection limit (LOD) is 0.09 ng / mL, a linear range (IC 20 -IC 80 ) is 0.29-19.30 ng / mL, and the nanobody has excellent organic solvent resistance. The nanobody Nb3-P-3 has an excellent application prospect in rapid detection of fludioxonil residues.

The invention discloses an anti-transferrin receptor (TfR1) antibody or an antigen binding fragment thereof. The preparation method comprises the following steps: carrying out phage immunization library-building screening by using a rabbit anti-technology to obtain an anti-TfR1 monoclonal antibody with high affinity, high specificity and high blood safety, and carrying out humanization and affinity maturation treatment on the anti-TfR1 monoclonal antibody to obtain the humanized anti-TfR1 monoclonal antibody which has high affinity and does not cause immunogenicity.

This invention relates to the field of biomedicine, and in particular to a T-cell receptor targeting MAGE-A3 and its applications. The T-cell receptor provided by this invention comprises six CDR regions: CDR1α, CDR2α, and CDR3α in the TCRα chain, and CDR1β, CDR2β, and CDR3β in the TCRβ chain, with amino acid sequences shown in SEQ ID Nos. 1-6, respectively. This invention utilizes reverse-locking engineering to modify wild-type MAGE-A3 TCR molecules, obtaining a highly efficient and non-toxic TCR targeting MAGE-A3, avoiding the toxic side effects caused by affinity maturation. This engineered TCR is then applied to the preparation of TCR-T cells for the treatment of solid tumors.

The present invention provides affinity matured recombinant monoclonal antibodies (mAbs) and fragments that bind specifically to an HLA-E- peptide complex, including HLA-E-VL9 complexes, and regulate the cytotoxicity effector cell function of NK. Herein, monoclonal antibodies were recombinantly derived from isolated functional HLA-E-VL9-specific mAbs from the naïve human B cell repertoire. Such antibodies are capable of regulating effector cell cytotoxicity and can preferentially recognize HLA-E-VL9 peptide complexes expressed on the surface of tumor cells. The monoclonal antibodies were subject to one or more rounds of affinity maturation. The invention provides methods for using affinity matured HLA-E-VL9 mAbs to modulate NK cell function as part of immunotherapeutic strategies.

The disclosure provides methods for promoting affinity maturation, and in particular in vivo affinity maturation, of antibodies. The disclosure also provides a system of affinity maturation of an antibody as well as compositions comprising antibodies generated from methods described herein and polynucleotides encoding such systems.

The application belongs to the technical field of biological medicine, and specifically discloses a single-domain antibody against human MMP-1, a mesenchymal stem cell exosome targeted and modified by the single-domain antibody, and application of the single-domain antibody and the exosome in repairing skin photoaging. The surface of the exosome is covalently connected with the single-domain antibody that specifically targets human MMP-1 through click chemistry technology, the single-domain antibody has an amino acid sequence as shown in SEQ ID NO:1, and is obtained through camel phage display library screening and affinity maturation, and has a high affinity of a nanomolar level to MMP-1. The preparation method comprises screening and expression of the single-domain antibody, extraction and purification of the mesenchymal stem cell exosome, and directional coupling through DBCO-azide click chemistry. The modified exosome can specifically recognize and enrich in photoaged skin tissue, significantly inhibit collagen degradation, promote extracellular matrix reconstruction, relieve oxidative stress and inflammatory response, and exhibits excellent effects in repairing skin photoaging caused by ultraviolet rays, and is suitable for development of skin repair drugs and cosmetics.

This document relates to methods and materials involved in producing antibodies (e.g., single domain antibody (sdAbs) and / or heavy chain only antibodies) having one or two chimeric heavy chains. For example, (A) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having one or two chimeric heavy chains that include (1) a non-human Ig heavy chain constant domain (CH) 2 and / or a non-human CH3 domain and (2) a VH domain such as a VH domain set forth in any one of SEQ ID NOs:74-87. (B) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce antibody-like molecules that include (1) a non-human heavy chain constant (CH) 2 domain and / or a non-human CH3 domain (e.g., endogenous CH2 and / or CH3 domains) and (2) a TCR variable domain (e.g., a human TCR variable domain). (C) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce antibody-like molecules that include (a) a first amino acid sequence of a FN3 polypeptide (e.g., a 10FN3 polypeptide). (b) a human Ig variable D domain, (c) a second amino acid sequence of a FN3 polypeptide (e.g., a 10FN3 polypeptide), and (d) a non-human Ig heavy chain CH2 domain and / or a non-human CH3 domain (e.g., endogenous Ig CH2 and / or CH3 domains), (D) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having one or two chimeric heavy chains that include (a) a non-human Ig heavy chain constant domain (CH) 2 and / or a non-human CH3 domain and (b) a variable region that includes a human JH domain (e.g., a human JH3 domain or a human JH4 domain) lacking all or at least one tryptophan amino acid residue(s), and (E) genetically engineered non-human animals (e.g., genetically engineered mice) having the ability to produce an antibody having a modified heavy chain including (a) a non-human CH2 domain and / or a non-human CH3 domain (e.g., endogenous CH2 and / or CH3 domains) and (b) a variable region that includes a human VH domain having a FR2 containing one, two, three, four, or more amino acid are provided. In addition, chimeric non-human animals (e.g., mice) generated from an embryo having (a) a first cell having one or more genomic modifications that prevent the first cell (and cells derived from the first cell) from producing immunoglobulins and (b) a second cell having an IgH locus that includes an exogenous nucleic acid sequence encoding a heavy chain variable region of an antibody of interest such that the chimeric non-human animal produces heavy chain antibodies containing the heavy chain variable region of the antibody of interest in addition to one or more variants of those heavy chain antibodies that underwent in vivo affinity maturation are provided.