Development of specific nanobodies (VHH) for CD19 immuno-targeting of human B-lymphocytes

Objective(s): CD19 is a transmembrane glycoprotein of immunoglobulin superfamily. In order to treat lymphoma, monoclonal antibodies (mAb) can target different antigens, including CD19, CD20 and CD22 on the surface of B-cells. Along with biotechnology progress, a new generation of antibodies is introduced, with the purpose of eliminating the defects of the previous generation. Among the most developed one are nanobodies (Nb).  Nbs are a unique kind of camelid single domain antibody fragments with a broad range of medical applications. Unique physicochemical properties of Nbs have made them ideal candidates for therapeutic and diagnostic applications. Materials and Methods: An immune gene library was created, and several CD19 specific Nbs were selected through antigen panning process, and their molecular properties as well as specificity, sensitivity, affinity and immunoreactivity against CD19 positive and negative cells were evaluated. Results: The Nb library was prepared with 7.2 x107 members. We managed to isolate a panel of CD19-specific Nbs after the last round of selection with the affinity of isolated Nbs being estimated at the standard range of 15-35 nM.  Sequence analysis of positive clones was indicative of the fact that 12 variable sequences were confirmed. Of all these 12 clones, 2 clones with the greatest level signal in ELISA underwent subsequent analysis. Our sequencing results indicated high sequence homology (approximately 90%) between the Nb and Homa variable immunoglobulin domains.Conclusion: Specific Nbs possess the potential to be used as novel therapeutic approaches in order to treat autoimmune diseases and B-cell lymphoma

The Lack of Historical Struggle and Defeat of Constitutionalism in Iran (Mashroutiat)

The theory of progress of constitutionality(Mashroutiat) which was aptly named “the new threshold” was aimed to lay the basis for constitutionalism by limiting the State. But the constitutionality didn’t last long and “the great misfortune” of the King Reza was formed out of it. Our question in the present research is the reason why all the great hopes of the constitutionalists and the intellectuals ran to waste and the historical reality that brought the country to the verge of destruction convinced the people that a central authoritarian state should be created. The explanation of the failure of the theory of progress is possible through the study of the relation between this era’s thought system, the thought tradition in Iran and the thought of the European Modernity. The fact that what eventually was the end of this thought system of constitutionalism in relation to the historical reality and consequences it had for Iran is the main aim of this article. The theory of progress-modernization in Iran had totally new epistemic foundations in comparison with the traditional “narratives” in Europe tried to constitute the Modernity on the basis of the western thought’s appearances. By reducing “the Metanarrative of Emancipation” in the thought of the European intellectuals they reduced that to freedom from despotism. Trying to find the legitimacy of these new institutions in tradition led to the formation of a returning model of the logic of transformation of the structure of political thought in Iran with which the political events conformed necessarily