|
|
Preparation of a polymeric therapeutic targeting CD20 positive B-lymphomas and NK cells
Hejl, Maxmilián ; Vaněk, Ondřej (advisor) ; Bělonožníková, Kateřina (referee)
Malignant transformation of B-cells is manifested by a marked increase in the number of surface markers 20 (CD20, cluster of differentiation 20). In studying this trend, chimeric monoclonal antibodies targeting CD20 were introduced to induce apoptosis in B-lymphomas. Since the introduction of the first therapeutic monoclonal antibody rituximab, many others have been developed, with some still used to treat B-lymphomas today. Unfortunately, in many cases, resistance to these drugs is developing, and therefore the development of new types of therapeutics is still relevant. This work aims to develop a polymer-protein macromolecular conjugate capable of inducing apoptosis in CD20 positive leukemia cell lines. For this purpose, we work with biologically active vectors, so-called anti-CD20 nanobodies. This is a variable binding domain derived from the "heavy chain only" antibodies found in, e.g., llamas or camels. Compared to conventional antibodies, nanobodies are approximately ten times smaller, but their binding affinity for the antigen is not altered. For this reason, nanobodies are ideal candidates for attachment to a polymeric carrier, where poly-N-[2-(hydroxypropyl)methacrylamide] (pHPMA) was chosen in this work. The transpeptidase reaction catalyzed by recombinant sortase A, which recognizes and...
|
guest ::
