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EGFR-CD3 bifunctional antibody and application thereof

ActiveCN111848806APromote differentiation and proliferationLow immunogenicityHybrid immunoglobulinsAntibody ingredientsCD3Molecular biology
The invention provides an EGFR-CD3 bifunctional antibody. The bifunctional antibody comprises two same light chains and two same recombinant heavy chains, wherein the amino acid sequence of each lightchain is as shown in SEQ ID NO. 8, each recombinant heavy chain is formed by connecting an EGFR antibody heavy chain and a single-chain antibody scFv of CD3 protein through a linker sequence; the amino acid sequence of the EGFR antibody heavy chain is as shown in SEQ ID NO. 7; the amino acid sequence of the linker sequence linker is as shown in SEQ ID NO. 9; the amino acid sequence of the single-chain antibody scFv of the CD3 protein is shown as any one of SEQ ID NO.1, SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4, SEQ ID NO.5 or SEQ ID NO.6. The EGFR-CD3 bifunctional antibody can be specifically combined with human CD3 protein and EGFR, the immunogenicity of the murine antibody can be reduced, T cells can be effectively activated, the binding of human EGFR and EGFR can be blocked, the bifunctional antibody can be anchored on the surface of tumor cells by binding with EGFR, and can activate T cells by binding with CD3 so as to achieve the tumor cell killing purpose.
Owner:广东安普泽生物医药股份有限公司

PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) resistant monoclonal antibody

The invention relates to the technical field of antibody engineering and in particular discloses a PCSK9 (Proprotein Convertase Subtilisin Kexin Type 9) resistant monoclonal antibody. The monoclonal antibody disclosed by the invention comprises an amino acid sequence coding an antibody variable region and a CDR region. The invention further discloses an acquiring method and application of the monoclonal antibody. The method comprises the following steps: screening a PCSK9 resistant monoclonal antibody from a phage antibody library, performing affinity maturation through a method for constructing the phage antibody library by virtue of strand displacement, performing mutant library-construction screening on light-chain CDR1, 2 and 3 regions of the monoclonal antibody obtained by preliminaryscreening, selecting a monoclonal antibody with high affinity, performing mutant library-construction screening on heavy-chain CDR1, 2 and 3 regions of the monoclonal antibody, and finally screeningthe PCSK9 resistant monoclonal antibody with high affinity. The PCSK9 resistant monoclonal antibody obtained in the invention has excellent affinity to PCSK9, is capable of inhibiting binding betweenthe PCSK9 and ligands thereof, and can be used for treating dyslipidemia, cardiovascular and cerebrovascular diseases and thrombosis-obstructive diseases.
Owner:BEIJING DONGFANG BIOTECH

Sclerostin and the inhibition of wnt signaling and bone formation

The loss of the SOST gene product sclerostin leads to sclerosteosis characterized byihigh bone mass (HBM). In this report, we found that sclerostin could antagonize canonical, Wnt signaling in human embryonic kidney A293 cells and mouse osteoblastic MC3T3 cells. This sclerostin-mediated antagonism could be reversed by over-expression of Wnt coreceptor LRP5. In addition, we found that sclerostin bound to LRP5 as well as LRP6 and identified the first two YWTD-EGF repeat domains of LRP5 as being responsible for the binding. Although these two repeat domains are required for transducing canonical Wnt signals, canonical Wnt did not appear to compete with sclerostin for binding to LRP5. Examination of the expression of sclerostin and Wnt7b, an autocrine canonical Wnt, during primary calvarial osteoblast differentiation revealed that sclerostin is expressed at the late stages of osteoblast differentiation coinciding with the expression of osteogenic marker osteocalcin and trailing after the expression of Wnt7b. Given the plethora of evidence indicating that canonical Wnt signaling stimulates osteogenesis, we believe that the HBM phenotype associated with the loss of sclerostin may at least in part be attributed to an increase in canonical Wnt signaling resulting from the reduction in sclerostin-mediated Wnt antagonism.
Owner:UNIV OF CONNECTICUT
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