Search results for: Mouse Anti-Human Liver Ag. Antibodies
#34477814 // To Up
Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction.
Orthologous proteins contain sequence disparity guided by natural selection. In certain cases, species-specific protein functionality predicts pharmacological enhancement, such as greater specific activity or stability. However, immunological barriers generally preclude use of nonhuman proteins as therapeutics, and difficulty exists in the identification of individual sequence determinants among the overall sequence disparity. Ancestral sequence reconstruction (ASR) represents a platform for the prediction and resurrection of ancient gene and protein sequences. Recently, we demonstrated that ASR can be used as a platform to facilitate the identification of therapeutic protein variants with enhanced properties. Specifically, we identified coagulation factor VIII (FVIII) variants with improved specific activity, biosynthesis, stability, and resistance to anti-human FVIII antibody-based inhibition. In the current study, we resurrected a panel of ancient mammalian coagulation factor IX (FIX) variants with the goal of identifying improved pharmaceutical candidates. One variant (An96) demonstrated 12-fold greater FIX activity production than human FIX. Addition of the R338L Padua substitution further increased An96 activity, suggesting independent but additive mechanisms. after adeno-associated virus 2 (AAV2)/8-FIX gene therapy, 10-fold greater plasma FIX activity was observed in hemophilia B mice administered AAV2/8-An96-Padua as compared with AAV2/8-human FIX-Padua. Furthermore, phenotypic correction conferred by the ancestral variant was confirmed using a saphenous vein bleeding challenge and thromboelastography. Collectively, these findings validate the ASR drug discovery platform as well as identify an ancient FIX candidate for pharmaceutical development.Kristopher A Knight, Christopher W Coyle, Caelan E Radford, Ernest T Parker, Andrew Fedanov, Jordan M Shields, Fania Szlam, Anatolii Purchel, Michelle Chen, Gabriela Denning, Roman M Sniecinski, Pete Lollar, H Trent Spencer, Eric A Gaucher, Christopher B Doering
1328 related Products with: Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction.
60 IU0.1mg10 0.1mg40 IU2 0.5mg1mg20 IU0.5mg100.00 ugOne 96-Well Strip MicroplRelated Pathways
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#2768218 // To Up
Production and characterization of monoclonal antibodies to rat liver arginase.
Rat liver arginase was purified and five monoclonal antibodies were produced by fusion of spleen cells from a Balb/c mouse and the myeloma cell line P3-X36-Ag-U1. One, R2D19, of five antibodies belonged to the IgG2a subclass, the other four, R1D81, R1G11, R2E10, and R2G51, were of the IgG1 type. The R1D81 cross-reacted with human liver arginase. This antibody inhibited the arginase activity, competing with arginine. These results suggest that R1D81 binds to the catalytic site of arginase. The R2D19 also inhibited the enzyme activity but acted as a noncompetitive inhibitor. With the use of R1D81 and a polyclonal anti-human liver arginase antibody conjugated with alkaline phosphatase, a sandwich enzyme-linked immunosorbent assay (ELISA) was developed for the quantification of human arginase. Specificity of monoclonal antibodies for rat liver arginase was examined by means of the sandwich ELISA. Eight pairs of monoclonal antibodies could form a sandwich with the arginase. Only the R2E10 could be used for both the first and the second antibody in the sandwich system. In other cases, monoclonal antibodies could not be interchanged between solid and liquid phase.A Isoai, S Harie, K Uchida, H Hirai
1781 related Products with: Production and characterization of monoclonal antibodies to rat liver arginase.
200 ug0.1 mg200 ug200 ug1 mg200ug100 ug200 ug100 ug200 ug100.00 ug100 ugRelated Pathways
#6373821 // To Up
Characterization of three restricted specificity monoclonal antibodies raised against the human glioma cell line D-54 MG.
Monoclonal antibodies ( MCAs ) have been derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells and splenocytes immunized to human glioma cell line D-54 MG. MCAs 2F3 , 4C7 , and 5B7 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-anti-peroxidase (PAP) immunohistology of unfixed tissue samples. MCA 2F3 exhibits the most highly restricted pattern of reactivity we have observed, reacting only with 5/12 glioblastoma cell lines and 1/4 fetal skin lines by CS-RIA, and to 9/11 glioblastoma tissue samples by PAP and absorption analysis; this MCA is totally nonreactive with melanomas, neuroblastomas, meningiomas, and control non-central nervous system tumors, and to adult and fetal tissues including brain, thymus, spleen, liver, lung, heart, gut, skin, and muscle by PAP analysis. MCAs 4C7 and 5B7 demonstrate neuroectodermal tumor cross-reactivity profiles, reacting with either melanomas ( 5B7 ) or melanomas and neuroblastomas ( 4C7 ); both are reactive with fetal skin, brain, and thymus of less than or equal to 16 weeks of gestational age. Other than this latter fetal antigen reactivity, these MCAs share the same negative reactivity profile described above for MCA 2F3 . Data from experiments using control or 0.02% EDTA-treated confluent cell monolayers of D-54 MG as antibody absorbents showed that the antigens detected are present in the extracellular matrix material remaining following cell removal. The data presented here establish that these highly restrictive anti-human glioma cell line MCAs are expressed in primary human gliomas; that the markers defined are developmental in nature, in that they are expressed by human fetal tissue, but not by adult tissue; and that in conjunction with previously characterized specificities, these markers of antigenic heterogeneity will be valuable in model system studies of therapeutic response heterogeneity.C J Wikstrand, S H Bigner, D D Bigner
1530 related Products with: Characterization of three restricted specificity monoclonal antibodies raised against the human glioma cell line D-54 MG.
1 mg25 100 ug1 mg100.00 ug100 μg0.2 mL0.5 ml200.00 ugRelated Pathways
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